http://cmb.ornl.gov

Center for Molecular Biophysics

2006-2011
CMB is affiliated with the Biosciences Division of the Energy and 

Engineering Sciences Directorate at ORNL and with the Department 

of Biochemistry and Molecular and Cellular Biology in the College of 

Arts and Sciences at UT, and we thank these organizations for putting up with us and our griping over the last five years! Everything we 

have accomplished was enabled by our systems administrators, Michael Galloway and Steve Moulton, and our secretary, Julia Cooper.
Welcome!

The University of Tennessee (UT) / Oak Ridge National Laboratory (ORNL) 

Center for Molecular Biophysics (CMB), was founded in October 2006. With an 

approximately 50/50 UT/ORNL personnel mix, we have now built up a vibrant 

research atmosphere. 

Thematically, our research is heavily influenced by the ‘mission space’ of ORNL 

and DOE. Supercomputing and neutron scattering constitute central toolsets 

that we integrate into our investigations in bioenergy and subsurface biogeochemistry. At the same time, we also have programs in biomedical sciences, 

including drug design. Our research is strongly interdisciplinary, incorporating 

elements of theoretical physics, quantum chemistry, statistical mechanics and 

simulation methodologies through to molecular and synthetic systems biology. 

Our team of principal investigators comprises myself, three other UT professors 

and three ORNL Staff Scientists. We have two UT Assistant Professors: Jerome 

Baudry, who specializes in ligand binding and computational biochemistry, 

and Tongye Shen, who is more physics-oriented. Jerome and Tongye have, in 

a relatively short period of time, already established productive programs and 

published several significant papers. Hong Guo, an Associate Professor who I 

first met twenty-eight years ago in Martin Karplus’ group at Harvard, specializes 

in enzyme reaction mechanisms. 

The first ORNL staff scientist to be hired, in 2008, was Xiaolin Cheng, and 

two more have been recently appointed, Jerry Parks and Loukas Petridis. 

Again, these three have complementary expertise, with Xiaolin experienced 

in simulation methodologies and ion channels, Loukas coming from polymer 

physics, and Jerry a quantum chemist. 

The above team of principal investigators has worked together with our 

postdoctoral fellows, graduate and undergraduate students to produce 17 

successful grant proposals and about 130 peer-reviewed publications in the 

last five years. The publications include reports on a number of breakthroughs 

in fields of research of national importance, and some of the corresponding 

press releases by UT or ORNL are reprinted here. Our research, as well as the 

challenges ahead, is discussed here in an informal style from the point of view 

of the young scientists who actually did the work. 

I hope you find our five-year report a stimulating read! 

Jeremy C. Smith, Director, CMB.
Hanging: Jeremy Smith

Standing: Zheng Yi, Xiaolin Cheng, Tongye Sheng, Hong Guo, Qin Xu, Vonel Teragene, Ricky

Nellas, Richard Lindsay, Derek Cashman, Jerome Baudry, Ryan Johnson, Barmak Mostofian, 

Hao-Bo Guo, Jerry Parks, Demian Riccardi, John Eblen, Goundla Srinivas, Steve Moulton, Nikolai Smolin

Sitting: Julia Cooper, Barbara Collignon, Xianghong Qi, Liang Hong, Amandeep Sangha, Loukas 

Petridis, Yinglong Miao
Table of Contents

Principal Investigators

Research Highlights

Bioenergy – The Recalcitrance of Plants

Supercomputing – Towards the Exascale

Neutron Scattering – 

Structure and Dynamics of Biomolecular Systems

Subsurface Biogeochemistry – 

Transport and Transformation of Mercury

Biomedical Research

Enzyme Catalysis - Faster Please

Multiscale Methods - Scaling from Atoms Upwards

How does a Physicist Survive in a Biology Department?

ORNL over the Decades

Five Germans in Tennessee

Publications

Staff

CMB External Funding

Supercomputer Allocations

Awards

2

4

6

12

15

18

20

28

30

34

36

38

44

52

54

56

59

1
Principal Investigators

Of the center for Molecular Biophysics

Jerome Baudry

Assistant Professor, Department of Biochemistry and Cellular and 

Molecular Biology, University of Tennessee, Knoxville

Jerome received a Ph.D. in molecular biophysics from the University of ParisVI. After his postdoctoral work in the group of Klaus Schulten at the University 

of Illinois, Dr. Baudry worked in the pharmaceutical industry and as Research 

Faculty in the School of Chemical Sciences at the University of Illinois, UrbanaChampaign. Jerome joined the Center for Molecular Biophysics as tenure-track 

faculty in 2008. His group conducts research on the biophysics of protein/

ligand and protein/protein interactions and develops supercomputing tools to 

accelerate drug discovery, using these tools in specific health and environmental discovery projects. Jerome is also active in obtaining fundamental understanding of intermolecular 

interactions.

Xiaolin Cheng

Staff Scientist and Joint Assistant Professor, ORNL Computer Science 

and Mathematics Division

Xiaolin is a Staff Scientist in the Computer Science and Mathematics Division 

at Oak Ridge National Laboratory. He is also a joint Assistant Professor in the 

Department of Biochemistry & Cellular and Molecular Biology at the University 

of Tennessee, Knoxville. He received his Ph.D. from the State University of New 

York at Stony Brook, and his postdoctoral training at University of California, 

San Diego. Moving to ORNL in early 2008 Xiaolin’s research has been focused 

on developing more scalable and multi-scale algorithms for molecular simulation on emerging computer architectures and the application of molecular 

simulations to understanding biomass recalcitrance, gating mechanisms in ion channels and drug 

resistance of HIV integrase.

Hong Guo

Associate Professor, Department of Biochemistry and Cellular and 

Molecular Biology, University of Tennessee

Hong obtained his Ph.D. from Harvard University in 1991. He was an International NSERC Fellow at the University of Waterloo, Canada in 1991-1993, a 

Research Associate at CERCA/University of Montreal, 1994-1997 and returned 

to Harvard as a scientist 1998-2001. He has lead a research group at Department 

of Biochemistry & Cellular and Molecular Biology, University of Tennessee 

since 2002. He has performed and directed research in computational studies 

of proteins, the catalytic mechanisms of enzymes, the role of hydrogen bonding and other interactions on protein structure and stability, and structural and 

vibrational properties of small molecules.

jbaudry@utk.edu

chengx@ornl.gov

hguo1@utk.edu

2
Jeremy C. Smith

UT/ORNL Governor’s Chair and Director of the Center for Molecular 

Biophysics

Jeremy received a Ph.D. from the University of London in 1985. He was a postdoctoral fellow at Harvard University, 1985-1989. He previously lead research 

groups in biomolecular simulation at the Centre D’Etudes Nucleaires at Saclay, 

France, 1989-1998 and as Chair of Computational Molecular Biophysics at the 

University of Heidelberg, Germany, 1998-2006. He sticks his nose into a lot of 

research performed at CMB including the high-performance computer simulation of biological macromolecules, neutron scattering in biology, the physics 

of proteins, drug design, bioenergy, subsurface biogeochemistry and the analysis of structural change 

in proteins. As of 2011 Smith has published close to 300 peer-reviewed scientific articles.

smithjc@ornl.gov

Tongye Shen

Assistant Professor, Department of Biochemistry and Cellular and 

Molecular Biology, University of Tennessee Knoxville

Tongye received a Ph.D. in physics from the University of California-San Diego 

in 2002. He was a postdoctoral researcher at the Center for Theoretical Biological Physics at UCSD, 2003-2007 and a postdoctoral associate at the Center for 

Nonlinear Dynamics/Theoretical Biology and Biophysics Group, Los Alamos 

National Laboratory, 2007-2009. Tongye has constructed physical models and 

performed theoretical calculations and simulations on various biomolecular 

systems, ranging from the internal conformational dynamics of proteins and 

polysaccharides and protein-ligand association, to larger cellular structures. As 

of 2011, Tongye has published 40+ peer-reviewed scientific articles.

tshen@utk.edu

Loukas Petridis

Staff Scientist, ORNL Biosciences Division

Loukas received a Ph.D. in physics from the University of Cambridge in 2006. 

He was a postdoctoral fellow at ORNL, 2007-2009. His research focus is computer simulation of biological macromolecules, neutron scattering and polymer theory with emphasis in bioenergy and his current projects include the 

dynamic visualization of lignocellulose, a simulation model of lignocellulosic 

biomass deconstruction, and incorporating molecular-scale mechanisms stabilizing soil organic carbon into terrestrial carbon cycle models. petridisl@ornl.gov

Jerry M. Parks

Staff Scientist, ORNL Biosciences Division

Jerry received a Ph.D. in Chemistry in 2008 from Duke University. Previously 

a postdoctoral researcher at ORNL from 2008 to 2009, his research interests 

include using computer simulation to study the structure and dynamics of biomolecules, bioinorganic chemistry of mercury, and enzyme mechanisms.

parksjm@ornl.gov

3
Research Highlights

Bioenergy

Folding & Function

Multiscale

Lignin surface structure

Hydrogen-bonding in cellulose deconstruction

Catalytic mechanism of cellulose degradation by a cellulase

Solvent-free coarse-grain model for cellulose fibrils

Acetate- and ethanol-tolerant biomass-degrading microbe strains

Dehydration-driven solvent exposure of hydrophobic 

surfaces drives folding

Loop-closure kinetics and structured folding pathways

Accurate peptide partitioning and folding into lipid bilayers

Sugar recognition by ricin-like domains

Hydration, energetic roughness and peptide dynamics

Ion Channels and the Nicotinic Acetylcholine Receptor

REACH – coarse-graining biomolecular dynamics

Transition networks, metastable states and dynamical 

fingerprints of proteins

4 Treecode fast electrostatics
5

Medicine

Catalysis

Neutron Scattering

Supercomputing

Subsurface Biogeochemistry

Rapid docking of ligands on supercomputers and cloud architectures

Molecular origin of Gerstmann-Sträussler-Scheinker syndrome

Catalytic mechanisms of

•	 a carboxyl peptidase

•	 xyloglucan endotransglycosylases/hydrolases

•	 a methyl transferase 

Lattice dynamics of a protein crystal

Subdiffusion and fractal configuration space

Three classes of motion in the neutron-scattering spectrum of a globular protein

Activity and dynamics of a very dry enzyme

Scaling of biological simulations on a petascale supercomputer 

Multimillion-atom simulations of biomass

Catalytic mechanism of an organomercurial lyase 

Dynamic mechanisms of bacterial mercury-resistance proteins
Bioenergy is of critical national 

importance as we strive to develop 

viable alternatives to fossil fuels. Our 

efforts in computer simulation and 

neutron scattering are aimed at 

understanding “biomass recalcitrance”.

Cellulose as a fuel source

“Biofuels serve as a substitute for a very 

important part of our current technology: combustion driven engines”, says 

graduate student Benjamin Lindner, 

who is performing simulations of biomass with the ORNL Jaguar supercomputer. “This work is also relevant when 

you consider national security, because 

it ensures that fuel will always be available albeit at a limited rate. Energy efficiency is another important aspect and 

a necessity for a sustainable economy. 

Cellulose-based biofuels have a significant advantage over first-generation 

biofuels, because they are more scalable, 

don’t compete with the food market, 

and allow the use of specially designed 

energy plants. However, it is unlikely 

that all our energy demands can be met 

by using biofuels. I see cellulose-based 

biofuels as an important ingredient in 

a sustainable and ecologically friendly 

energy mix.”

Bioenergy barrier

“Lignin is the major “undesirable” component of biomass in the conversion 

process”, adds Amandeep Sangha, a 

postdoctoral fellow. “The presence of 

lignin, along with other factors, makes 

the breakdown of polysaccharides into 

sugars difficult. Understanding the origin of biomass recalcitrance to hydrolysis is one of the major challenges in 

improving the efficiency of the conversion process.” 

According to Barmak Mostofian, also a 

graduate student, one of the main isBioenergy

the Recalcitrance of PlantS

CMB model of Lignocellulose. 

Cellulose (green) from plant 

cell walls binds strongly to 

other cell wall molecules 

such as lignin (in brown). 

Removal of lignin is essential 

for efficient biomass 

deconstruction.
Road to energy independence: 

Harnessing the sun to power 

greener vehicles and herald more 

efficient energy production.

sues, besides the frequently mentioned 

competition with food crops for available land and other logistics, is the development and proper implementation 

of technologies that produce affordable 

fuel in a more effective way. “While the 

enzymatic approach exploits the capabilities of natural catalysts to liberate 

sugars, which are then subsequently 

transformed into ethanol in a fermentation/distillation process, purely chemical routes do not rely on expensive 

enzymes or on the use of genetically 

altered microbes for enhanced alcohol 

production. Instead high-energy organic compounds can be synthesized 

directly from lignocellulose using solid 

catalysts, for instance. It is conceivable 

that the different approaches to tackle 

the natural resistance of biomass deconstruction will result in a multi-faceted bioenergy industry”.

ORNL Biofuels Science 

Focus Area and the Bioenergy Science Center

CMB is part of the Bioenergy Science 

Center (BESC), which integrates experts 

from a wide range of scientific disciplines to understand biomass recalcitrance. According to Loukas Petridis, “Most of the chemical data used to 

construct our lignocellulose (biomass) 

models are derived from experiments 

performed at BESC. Also, many fruitful ideas have arisen from interactions 

with experimentalists at BESC. For example, it was during a BESC retreat that 

I first saw beautiful images of lignin 

aggregates forming after dilute acid 

pretreatment of biomass. The subsequent study of lignin aggregation by 

computer simulation has been one of 

the main focus 

areas of bioenergy research performed 

in the first 5 years of CMB” (see press 

release on following page).

BESC and the ORNL Biofuels Science 

Focus Area aim to provide breakthroughs that will allow viable cellulosic biofuel production. Significant 

steps in this direction have already 

been achieved. CMB has participated 

in high-profile studies, commented 

on by Secretary Chu, identifying and 

characterizing a single microbial gene 

linked to increased ethanol tolerance. 

Also, Sangha and Jerry Parks have been 

performing quantum chemical calculations aiming at understanding lignin polymerization, and CMB has also 

performed calculations to understand 

cellulase catalysis and cellulosome 

function. 

According to Petridis, “In the next five 

years, BESC will use its achievements 

in order to viably produce biofuels. The 

way simulation can help is by providing 

detailed molecular-level understanding 

of mutated microbial proteins, or transgenic switchgrass. Such understanding 

enables rational improvement of these 

systems and thus helps us achieve improved bioethanol yield.”

7
OAK RIDGE, Tenn., June 15, 2011 — A

first of its kind combination of experiment and simulation at the Department of Energy’s Oak Ridge National 

Laboratory is providing a close-up look 

at the molecule that complicates nextgeneration biofuels.

Lignin, a major component of plant 

cell walls, aggregates to form clumps, 

which cause problems during the production of cellulosic ethanol. The exact 

shape and structure of the aggregates, 

however, have remained largely unknown.

ORNL neutrons, simulations reveal 

details of bioenergy barrier

Source: http://www.ornl.gov/info/press_releases/get_press_release.cfm?ReleaseNumber=mr20110615-00

New molecular models of lignin aggregates are helping scientists understand a limiting factor in the production of ethanol. (Image courtesy of http://www.scistyle.com)

8
A team led by ORNL’s Jeremy Smith 

revealed the surface structure of lignin 

aggregates down to 1 angstrom—the 

equivalent of a 10 billionth of a meter 

or smaller than the width of a carbon 

atom. The team’s findings were published in Physical Review E.

“We’ve combined neutron scattering 

experiments with large-scale simulations on ORNL’s main supercomputer 

to reveal that pretreated softwood 

lignin aggregates are characterized 

by a highly folded surface,” said Smith, 

who directs ORNL’s Center for Molecular Biophysics and holds a Governor’s 

Chair at University of Tennessee.

Lignin clumps can inhibit the conversion of biofuel feedstocks—for example, 

switchgrass—into ethanol, a renewable 

substitute for gasoline. When enzymes 

are used to release plant sugars necessary for ethanol production, the lignin 

aggregates bind to the enzymes and 

reduce the efficiency of the conversion.

Lignin’s highly folded surface creates more opportunities to capture the 

passing enzymes than a smooth surface would. An improved understanding of the lignin aggregates will aid 

scientists in efforts to design a more 

effective pretreatment process, which 

in turn could lower the cost of biofuels.

“Nature has evolved a very sophisticated mechanism to protect plants 

against enzymatic attack,” said ORNL

team member Loukas Petridis. “We’re 

trying to understand the physical basis 

of biomass recalcitrance—resistance of 

the plants to enzymatic degradation.”

The complementary techniques of 

simulation on ORNL’s Jaguar supercomputer and neutron scattering at 

the lab’s High Flux Isotope Reactor enabled Smith’s team to resolve lignin’s 

structure at scales ranging from 1 to 

1,000 angstroms. Smith’s project is the 

first to combine the two methods in 

biofuel research. “This work illustrates 

how state-of-the-art neutron scattering and high-performance supercomputing can be integrated to reveal 

structures of importance to the energy 

biosciences,” Smith said.

The research was supported by DOE’s 

Office of Science and used the resources of the Leadership Computing 

Facility at ORNL under a DOE INCITE

award. Team members include ORNL’s 

Sai Venkatesh Pingali, Volker Urban, 

William Heller, Hugh O’Neill and Marcus Foston and Arthur Ragauskas from 

Georgia Institute of Technology.

ORNL is managed by UT-Battelle for 

the Department of Energy’s Office of 

Science.

9
10
11

Ethanol tolerance in Clostridium thermocellum was 

traced to two mutations in a single gene encoding an 

alcohol dehydrogenase. A model of the enzyme with the 

mutation sites highlighted is shown here.
Supercomputing is a key element 

of the ORNL mission, alluded to by 

President Obama in his 2011 State of 

the Union speech. Also, UT recently 

joined the elite ranks of NSF supercomputing institutions with its Kraken 

machine. As molecular simulation 

is a CPU-hungry enterprise, CMB is 

keenly involved with the development and application of highly parallel codes and we are major users 

of the local supercomputers, having 

received several awards for supercomputing time, including from the 

prestigious DOE INCITE program. 

Here we ask John Eblen, a postdoctoral fellow, and Roland 

Schulz and Sally Ellingson, both 

graduate students, about their experiences with petaflop supercomputers and prospects as we 

move towards the exascale.

What is the most powerful 

computation you have 

ever performed?

Ellingson: I recently ran a highthroughput docking screen on the 

Jaguar machine that included over 

one million chemical compounds. We 

used an MPI (message passing interface) version of Autodock4 (virtual 

docking software) that distributes the 

docking tasks. 

Schulz: As part of our INCITE allocation, I am simulating lignocellulosic 

biomass. A realistic model requires 

several million atoms. Our largest 

model constitutes 22 million atoms 

and runs on 45,000 cores. Additionally, 

I run larger tests to improve software 

performance for current and future 

projects, and the largest of these was 

run on 150,000 cores. As far as I know 

this is a world record for this type of 

calculation.

D.E. Shaw has made a special 

purpose supercomputer for 

molecular simulation. How does 

ORNL’s Jaguar machine compare with it?

Schulz: The Shaw Anton special purpose machine is about 100 times faster 

for simulating the molecular dynamics of small biological systems, such as 

small proteins containing e.g. 20,000 

atoms. This is partly achieved by a network that is significantly faster. Jaguar 

allows us to run more flexible codes 

Supercomputing

Towards the Exascale
With a peak speed of 2.33 petaflops (over two thousand trillion calculations per second), “Jaguar,” a Cray XT5 supercomputer located 

at Oak Ridge National Laboratory, is one of the world’s fastest supercomputers for unclassified research. Capable of simulating physical systems with heretofore unfeasible speed and accuracy, Jaguar has led ORNL into the era of petascale computing and beyond.

and is more suitable for our very large 

simulations.

Are supercomputers easy to use 

for the average computational 

scientist?

Ellingson: When everything works 

right they are fairly easy to use. The 

hard part is figuring out what went 

wrong when it doesn’t work right.

What tools are you developing 

to help get programs to work on 

supercomputers?

Eblen: I’m focused on improving software development on supercomputers, a goal of the Eclipse Parallel Tools 

Platform (PTP) synchronized projects. 

Modern IDEs, such as Eclipse, offer 

many features to speed up software development. We want to make sure that 

these tools are available to those developing the most complex applications 

– those that run on supercomputers. 

Most people are not free to work directly on their favorite supercomputer 

with an IDE. They should be able to use 

the IDE on their personal computer, 

though, and have it work as if they 

were sitting at the supercomputer.

What have you done so far with 

the UT/ORNL supercomputers 

and what is the future for supercomputers in biomolecular 

simulation?

Schulz: We have performed enormous 

simulations of biomass that wouldn’t 

have been possible any other way. 

Analyzing the results is taking quite 

some time... 
Ellingson: I have done many smaller 

drug-design screenings to prepare 

for the million compound screen we 

recently completed. I think that we 

may see more special purpose computers, such as Anton, for biomolecular simulations. However, since special 

purpose computers are built around 

the code that runs on them, they will 

not be able to handle everything, and 

multi-purpose supercomputers will 

still be very important. Many multipurpose supercomputers are going 

toward hybrid architectures which 

include GPUs for part of the processing power. It will be important to learn 

how to correctly utilize these architectures to improve the speed of simulation code. 

How can we advance the state 

of software development, especially for supercomputing?

Eblen: Historically, leaps in what humans can do with computers come 

from newer and better tools. The 

purpose of a tool is to take care of the 

mundane activities, so that we can 

focus on the bigger issues. What has 

changed over time is what is considered “mundane.” Assemblers automate 

the mundane task of having to translate operations to bits and bytes. Compilers automate the mundane task of 

translating common operations to a 

series of assembly commands, such as 

adding multi-byte numbers or creating loops. IDEs automate still more 

complex operations. Each new class 

of tools frees us to tackle bigger, more 

ambitious projects. Unfortunately, 

this process has some inertia. People 

become familiar with their tools and 

aren’t eager to learn new ways of doing things. For example, some of our 

programming languages are long 

overdue for a remake. Now I love C++. 

It is my favorite of the commonly 

used languages. What other language 

allows both raw, system-level access 

and tons of useful, high-level features, 

such as classes and well-developed 

standard libraries? C++ is a good example of a tool that pushed the industry ahead. It suffers from its C heritage, 

though, which makes the language 

overly complex and error prone. Now 

there is a wonderful, relatively new 

language, called the D programming 

language, which has been carefully 

designed and well-engineered over 

about a decade now. It is a systems 

language that is just as powerful and 

feature-rich as C++ while fixing many 

of its problems. But I don’t know anyone trying to use it for supercomputing. So that is one example of a possible initiative that could advance our 

tools and increase even more of what 

we humans can do with our computers.

Mere mortals find computers 

extremely annoying when they 

don’t do what they want. Is it 

the same with you hot-shots?

Ellingson: Getting computers to do 

what you want is the fun part. If they 

always did exactly what you wanted 

the first time you tried, it wouldn’t 

be as rewarding when you finally get 

your programs working right.

Eblen: Of course! Often, I know why 

it’s not working like I want. So as a 

developer myself, depending on my 

mood and whatever the problem is, I

may feel sympathetic to the poor programmer or feel... displeased because 

he or she should have known better!

14
Neutrons are unique probes of condensed materials, furnishing both 

structural and dynamic information, 

and neutron scattering has been a sustained interest of Jeremy Smith’s since 

he published his first papers on the 

subject as a Ph.D. student at the Institut Laue-Langevin in Grenoble, France 

in 1986. The advent of the Spallation 

Neutron Source at ORNL now promises to take neutron scattering research 

to new heights, and we have therefore 

established a program aiming at developing methodologies for neutron research, integrating high-performance 

simulation with neutron scattering, 

and applying a range of neutron techniques to systems of interest in biology 

and the energy biosciences. 

The methodological work has produced a number of breakthroughs. 

Among these is the first calculation of 

the lattice dynamics of a protein crystal at atomic resolution, which we hope 

can at some point be tested experimentally using triple-axis instrumentation. Just this year, work performed 

principally by postdoctoral fellow 

Liang Hong, in collaboration with 

Alexei Sokolov, another Governor’s 

Chair, demonstrated how the dynamic 

neutron susceptibility of a protein can 

be simply interpreted in terms of three 

classes of motion (see press release). 

Complementary theoretical work with 

graduate student Thomas Neusius 

demonstrated that the subdiffusive 

behavior of peptide dynamics has a 

fractal origin.

Also, postdoctoral fellows Yi Zheng 

and Yinglong Miao have been working 

with Jerome Baudry and Nitin Jain, an 

Associate Professor in the UT Department of Biochemistry and Cellular and 

Molecular Biology, to perform and interpret neutron scattering experiments 

on cytochrome P450 – this work has 

led to a new method for analyzing elastic scattering that yields not only the 

average mean-square displacement of 

hydrogen atoms in a protein but also 

the variance.

Two growth areas for the future have 

been identified. One of these is the application of neutron spin-echo spectroscopy to characterize functional domain motions of biomolecules, an area 

that postdoctoral fellow Nikolai Smolin 

has been concentrating on, and the 

second is the application of neutrons 

to the energy biosciences, and, in 

particular, the structure and dynamics of lignocellulosic biomass. Finally, 

Jeremy would like to realize a vision 

of unifying exascale supercomputing 

with high-performance neutron scattering in which molecular simulations 

are performed using the full power of 

the exascale machinery and are used to 

plan and interpret experiments at SNS

in real time. We are quite a way from 

achieving that goal, but a first step 

has been taken by graduate student 

Benjamin Lindner, who has efficiently 

parallelized software for scattering 

calculations. Given the resources, the 

unification dreamed for will happen.

Neutron Scattering

Structure and Dynamics of Biomolecular Systems

15
OAK RIDGE, Tenn., Sep. 30, 2011 — Molecular motion in proteins comes in 

three distinct classes, according to 

a collaboration by researchers at the 

Department of Energy’s Oak Ridge 

National Laboratory and the University 

of Tennessee, in research reported in 

Physical Review Letters.

The research team, directed by ORNLUT Governor’s Chairs Jeremy Smith 

and Alexei Sokolov, combined highperformance computer simulation 

with neutron scattering experiments to 

understand atomic-level motions that 

underpin the operations of proteins.

High-performance simulation, neutrons 

uncover three classes of protein motion

Source: http://www.ornl.gov/info/press_releases/get_press_release.cfm?ReleaseNumber=mr20110930-00

Lysozyme (shown in blue) -- a natural enzyme found in 

tears, saliva and egg whites -- can break down bacterial cell 

walls (shown in pink). ORNL researchers have combined 

computational simulation and neutron experiments to 

clarify the complicated motions of proteins such as lysozyme into three distinct classes.

16
“The analysis and interpretation of 

neutron scattering spectra are always 

difficult for complex molecules such 

as proteins,” said Smith, who directs 

ORNL’s Center for Molecular Biophysics. “We’ve performed experiments and 

then shown that simulation can provide a clear view of them. It allows us 

to see through the complexity and find 

out what motions are going on.”

Defining the motions present -- localized diffusion, methyl group rotations 

and jumps -- is important as it allows 

scientists to think about how the motions determine the functions of proteins that are critical to all life.

“First, we found that experiment and 

simulation agreed perfectly with each 

other, which is remarkable,” Smith said. 

“Second, the simulations told us that 

this type of neutron scattering can be 

interpreted in a very simple way.”

Although the team performed its research on a particular protein called 

lysozyme, a natural antibacterial enzyme found in tears, saliva and egg 

whites, the researchers anticipate the 

technique will have a much broader 

impact in the neutron scattering community, aiding research in areas such 

as biofuel design or environmental 

remediation.

The combined simulation and neutron 

scattering approach should also be 

of use in the characterization of nonbiological materials such as polymers. 

Smith notes that approximately half 

the neutron scattering experiments at 

ORNL’s Spallation Neutron Source involve the study of motions in materials.

“These methods are of general applicability,” Smith said. “Many experimentalists can now come to the ORNL’s 

Spallation Neutron Source, measure 

a spectrum of whatever sample they 

have, and then apply this analysis in 

terms of three classes of motion to interpret their results.”

The research was primarily conducted 

by ORNL’s Liang Hong, with the support of Benjamin Lindner and Nikolai 

Smolin from ORNL. They performed 

neutron scattering experiments at 

ORNL’s Spallation Neutron Source on 

the BASIS instrument and at the National Institute of Standards and Technology Center for Neutron Research. 

The work was published as “Three 

classes of motion in the dynamic 

neutron scattering susceptibility of a 

globular protein.”

The simulation component of the work 

was supported by ORNL’s Laboratory 

Directed Research and Development 

program, while the neutron scattering component was supported by an 

Experimental Program to Stimulate 

Competitive Research (EPSCOR) grant 

to the University of Tennessee from 

the DOE Office of Science.

ORNL is managed by UT-Battelle for 

the Department of Energy’s Office of 

Science.

17
The fate of mercury as a subsurface 

contaminant is of particular interest 

in Oak Ridge because of contamination from cold-war activities at the 

Y12 weapons plant in the 1950s and 

1960s. It turns out that following 

mercury in the environment has some 

fascinating aspects. Mercury interacts 

with and is transformed by organic 

matter in streams and sediments, and 

bacteria are able to methylate mercury, rendering it more toxic, and also 

to demethylate and thus detoxify it. 

The transport and transformation of 

mercury in these bacterial cells has 

become a subject of intense interest for CMB, in the framework of 

an ORNL Science Focus Area and a 

university-led project through UT.

Among the methods applied are 

semi-empirical quantum mechanical/

molecular mechanical (QM/MM) calculations, which postdoctoral fellow 

Demian Riccardi has been working 

at streamlining, MD simulations and 

subsequent structural analysis, which 

Jerry Parks and postdoctoral fellow 

Hao-Bo Guo have performed. Also, 

Hong Guo and postdoctoral fellow 

Qin Xu are examining the chemistry of 

the reduction of mercury in a protein 

active site. All this work has involved 

intense (and sometimes heated!) collaboration with Profs. Anne Summers 

from the University of Georgia and 

Sue Miller of the University of California, San Francisco.

Why is mercury research 

important?

Parks: Mercury is interesting in itself 

because it’s a really shiny liquid metal 

that sticks to just about everything. 

Unfortunately, it also happens to be 

an environmental toxin. It really likes 

to interact with sulfur, which is one 

reason it is harmful to living organisms. Lots of bacteria are resilient 

and can live happily in mercury-rich 

environments. They have genes that 

allow them to take up harmful forms 

mercury from the environment and 

turn it into a less toxic form. But there 

are other types of bacteria that make 

the more toxic form called methylmercury. We need to understand the fate 

of mercury thoroughly – how it gets 

converted from one form to another by 

sunlight, bacteria, and so on. Mercury 

transformation not a one-time event 

- there is a complex global mercury 

cycle. So here’s how it works - There’s 

already some mercury hanging around, 

then more of it gets into the air from 

things like power plants, then it floats 

halfway around the world, falls back to 

the ground during a rainstorm, then it 

Subsurface Biogeochemistry

Transport and Transformation of Mercury

Mercury is an 

environmental 

toxin due to its 

unusually strong 

affinity for thiols 

and other functional groups.

18
Binding of Hg2+ to MerR induces conformational changes required to initiate transcription of Mer genes, which 

encode proteins and enzymes involved in mercury resistance. Two other major components of the Mer system 

are the organomercurial lyase, MerB, which converts methylmercury to Hg2+, and the mercuric reductase, MerA, 

which reduces Hg to Hg(0).

gets oxidized, then methylated, then 

demethylated, and then reduced and 

the whole process starts over again. 

What have you discovered about 

bacterial mercury transformation?

Hao-Bo Guo: “Mer” proteins are genetically encoded by the mer operon. 

These proteins transport and transform mercury in resistant bacteria. 

We have looked at the highly toxic 

form methylmercury – methylmercury – and how it is broken down by 

an enzyme called MerB. Another part 

of the molecular machinery is MerR, 

which turns on transcription of mer 

genes when mercury binds to it. Our 

recent work with X-rays, neutrons and 

MD simulations has shown that the 

primary motion of MerR involves two 

DNA-binding domains approaching 

and departing from each other. We 

successfully determined the end-states 

of this dynamics, and this may yield 

insight into other biological systems 

with similar dynamics.

What other aspects are worth 

pursuing?

Riccardi: The behavior of mercury is 

intimately related to its oxidation state 

and affinity for various ligands. We’re 

considering investigating how the 

oxidation state affects mercury transfer among ligands and across lipid 

membranes, and constructing model 

computational systems of naturally occurring organic matter to which mercury binds in streams. We’re also using 

structural bioinformatics to characterize both observed and potential sites 

of mercury interaction with biological 

molecules in vitro and in the crystalline state. All of these are very interesting research directions and could have 

broad scientific and environmental 

impacts.

19
Biomedical research expands in 

several directions at CMB. Using the 

ORNL and UT supercomputers to 

design new drugs is an important 

and exciting field. However, we 

are also researching bacterial 

chemotaxis, active site solvation 

and ion channel function:

Drug Design

Supercomputing and Docking 

CMB uses molecular modeling 

and computational chemistry to 

investigate how medically relevant 

biomolecules interact with each 

other. We are particularly interested in 

molecular discovery, i.e. how to select 

and/or design small molecules, like 

pharmaceuticals, that will interact in 

a specific and potent way with much 

larger molecules, like proteins. Small 

molecules may sometimes enhance, 

or sometimes inhibit, the functioning 

of the proteins to which they bind. To 

discover or design a new drug against 

a disease, we must understand a great 

deal about what the target proteins 

look like and how they function, such 

as where possible binding cavities 

are located in the protein, how these 

cavities change their shapes with 

time, and how the atoms in the 

proteins interact with those of the 

pharmaceuticals. 

The availability of thousands of 

processors, either localized together 

in a supercomputer, or delocalized as 

in cloud computing, can be used to 

perform virtual screening of massive 

databases of chemicals against 

protein targets. To take advantage 

of these giant computers, Jerome 

Baudry, postdoctoral fellow Barbara 

Collignon, Roland Schulz and Sally 

Ellingson have developed efficient, 

well validated computer programs 

for docking (see press release). Sally 

Biomedical Research

Using the power 

of supercomputers 

to accelerate drug 

discovery.
Ellingson is continuing this work and 

developing it for Cloud architectures 

and to allow multiple protein 

targets to be used efficiently in the 

docking process. It is now possible 

to investigate computationally how 

millions of compounds would bind in 

a given protein, or in multiple proteins 

of a biochemical pathway. These 

approaches are used in collaboration 

with experimental laboratories to 

discover novel classes of molecules 

against several endocrine cancers and 

infectious diseases. With the advent of 

the exascale in supercomputing, it may 

become possible to screen essentially 

complete ligand databases against all 

known classes of protein in about one 

day.

To improve the efficiency of drug 

design, it is very important to understand how drugs and proteins interact with each other at the atomistic 

scale. We are developing new views on 

how non-bonded interactions control the dynamics and the energetics 

of protein/ligand complexes through 

facilitation of molecular rotations and 

anion/π-interactions. We are also characterizing how medically and pharmaceutically important proteins are 

behaving, to understand how drugs 

may affect them: we are building the 

“protein skyscrapers” that control how 

bacteria look for food and we are following each and every water molecule 

that flushes a P450 enzyme’s active site 

to help detoxify drugs.

Detailed analysis of interactions within proteins - 

methyl groups probe local 

environments.

21

Detoxifyingenzymes 

cytochrome P450s 

“flush” their active 

site to ensure 

catalytic efficiency.
AIDS Drug Design

HIV-1 integrase is an important 

enzyme in viral HIV replication with 

apparently no human counterpart, 

making it an attractive therapeutic 

target for the clinical treatment of AIDS. 

Despite two decades of tremendous 

effort leading to promising integrase 

inhibitors, their binding modes remain 

elusive. The goal of this project, led 

by Xiaolin Cheng, is to understand 

at the molecular level the binding 

of potent inhibitors in the HIV-1 

integrase active site, and the structural 

mechanisms for drug-resistant viral 

mutants. Cheng is also using computer 

simulation to understand and predict 

from a statistical perspective the 

combinatorial mutation patterns 

responsible for HIV drug resistant 

mutants.

Active site of the HIV protein 

PFV integrase. 

22

Interactions in Proteins

The Baudry group is also interested in 

the effect of nonbonded interactions in 

protein-protein and protein-ligand complexes. Undergraduate student William 

Hembree has used quantum chemistry to 

investigate how the rotational dynamics 

of methyl groups, an important marker 

in chemistry, is affected by their microenvironment. In collaboration with the 

groups of Dr. Howell and Dr. Hinde at 

the University of Tennessee, the group, 

along with graduate student Jason Harris, is also investigating how anion/πinteractions in proteins and proteinligand complexes contribute to protein 

stability and dynamics.
Chemotaxis - 

Ligand based signaling pathways

Postdoctoral researcher Derek Cashman is working collaborative project 

involving the groups of Jerome Baudry 

and Igor Zhulin that involves the integration of bioinformatics with biophysical studies. The first step involves 

creating a natural classification of 

chemotaxis proteins based on phylogenetic analysis and identifying conserved residues within evolutionarily 

related subgroups, and co-variance 

analysis of co-evolving residues. This 

information is then integrated with 

machine learning analysis of surface 

patches on each protein to predict 

potential sites for protein-protein interactions, leading to molecular docking and computational simulations to 

test the protein-protein interactions of 

each model. These results will then be 

used to drive further experimental and 

systems biology research by our collaborators and other laboratories. The 

principles learned through these studies will provide insight into about signal transduction mechanisms, and will 

aid in the design of new therapeutics 

targeting the signaling pathways that 

control virulence in human pathogens.

23

The structural basis of bacterial chemotaxis. A hypothetical model of the bacterial chemoreceptor (MCP, shown 

in green) interacting with the scaffolding protein, CheW, and histidine kinase, CheA (both shown in blue). These 

proteins are part of a signal transduction cascade that responds to stimuli in the environment and transfers a 

signal to the bacterial flagellar apparatus to control the cell’s swimming behavior in response to that stimulus.
24

Simulation system with the human α7 nAChR 

receptor (ribbon) inserted into a lipid bilayer (licorice).

Solvation of Active Sites

P450 proteins are very important enzymes responsible in the human body 

that are responsible for processing 

many pharmaceuticals. Jerome Baudry 

and Postdoctoral researcher Yinglong 

Miao have used computer simulation 

to reveal the highly dynamic nature of 

CYP101 P450 hydration. Water molecules enter and leave the active site on 

the nanosecond timescale, sustaining 

the efficiency of the enzyme.

Channel gating and ligand 

recognition in pentameric 

ligand gated ion channels

The nicotinic acetylcholine receptor 

(nAChR) is a ligand-gated ion channel. Binding of neurotransmitter molecules to nAChR induces structural 

rearrangements of the membranespanning domain, which permits the 

influx of cations and leads to message 

propagation. Due to their essential 

roles in synaptic transmission, nAChRs 

have emerged as attractive therapeutic 

targets for the treatment of pain, cognitive impairment, neurodegenerative disease, schizophrenia, epilepsy, 

anxiety, and depression. Fundamental 

steps in receptor activation include 

neurotransmitter recognition, coupling of recognition to opening of 

the ion pore, and passive flow of ions 

through the pore. Xiaolin Cheng has 

performed extensive molecular dynamics simulations to understand the 

molecular mechanisms underlying 

all three of these fundamental steps. 

Cheng’s calculations probe the energy 

barriers to ion conduction and origins 

of ion selectivity in the channel. 
Jeremy Smith, Governor’s Chair for Molecular Biophysics at the University of 

Tennessee, Knoxville, has helped reveal 

a key trigger of Gerstmann–Sträussler–

Scheinker (GSS) syndrome, a rare but 

deadly neurodegenerative disease. The 

finding could have far-reaching implications for the treatment of other neurodegenerative diseases such as Alzheimer’s, 

Huntington’s, and Parkinson’s.

Smith conducted his research with two 

collaborators in Italy: Isabella Daidone, 

a former postdoctoral researcher of his 

who is now at the University of L’Aquila, 

and Alfredo Di Nola of Sapienza – Università di Roma.

Most GSS patients begin developing 

symptoms in their late fifties. Symptoms include loss of memory, difficulty 

speaking, and unsteadiness and lead to 

progressive dementia, and then death 

within a few months or years. There 

is presently no cure or treatment. The 

disease results from a single, tiny mutation in a protein, resulting in it having a wrong shape—through “misfolding”—then aggregating to form amyloid 

plaques in the brain.

“Ever since the ‘mad cow’ scare in Britain 

in the 1990s, which led to several hundred human deaths and 4.4 million cattle 

being destroyed, I’ve been interested in 

finding out more about these fascinating diseases of wrongly shaped proteins,” 

said Smith, who was born in England.

The team compared high-performance 

computer simulations of the structures of the normal and the GSS–mutant 

proteins. They found the GSS protein 

looks dramatically different from the 

normal form and revealed how its shape 

is primed for plaque formation.

“This research shows how computer simulation can be used to pinpoint changes 

in molecular structure that lead directly 

to disease,” said Smith. “We think that a 

similar line of investigation should prove 

beneficial in understanding the origins 

of other amyloid diseases such as Alzheimer’s, Parkinson’s, and rheumatoid 

arthritis. Once the origin is understood 

at molecular detail, strategies to rationally prevent and cure a disease can be 

conceived.”

The findings can be found in the article, “Molecular Origin of Gerstmann–

Sträussler–Scheinker Syndrome: Insight 

from Computer Simulation of an Amyloidogenic Prion Peptide” in this month’s 

edition of the Biophysical Journal.

The research was funded in part by a Marie Curie grant from the European Union.

UT Scientist Uncovers Trigger to Fatal 

Neurodegenerative Disease

Source: http://www.utk.edu/tntoday/2011/06/22/jeremy-smith-gss-protein

25
A team led by Jerome Baudry of the 

University of Tennessee-ORNL Center for Molecular Biophysics adapted a 

widely used existing software to allow 

supercomputers such as ORNL’s Jaguar to sift through immense molecular 

databases and pinpoint chemical compounds as potential drug candidates.

The research was published in the 

Journal of Computational Chemistry 

as “Task-parallel MPI implementation 

of Autodock4 for docking of very large 

databases of compounds using High 

Performance Super-Computers.”

Supercomputing Research Opens 

Doors for Drug Discovery

Source: http://www.sciencedaily.com/releases/2010/12/101209164146.htm

A quicker and cheaper technique to scan molecular databases developed at the 

Department of Energy’s Oak Ridge National Laboratory could put scientists on the 

fast track to developing new drug treatments.

Supercomputers could help speed up the drug discovery process by identifying suitable 

chemicals (seen as gray spheres) that can dock onto a designated target in the body, such 

as a protein (seen as red ribbons). (Credit: Image courtesy of DOE/Oak Ridge National 

Laboratory)

26
“Our research is the missing link between supercomputers and the huge 

data available in molecular databases 

like the Human Genome Project,” 

Baudry said. “We have an avalanche of 

data available to us, and now we need 

to translate that data into knowledge.”

Such translation is critical for the first 

stages of drug development, in which 

researchers look for appropriate chemicals that interact with a target in the 

body, typically a protein. If the chemical is suitable, it attaches onto the 

protein and produces a desirable effect 

in the cell.

But with thousands of known proteins 

and millions of chemicals as potential 

drugs, the number of possible combinations is astronomical.

“It is very expensive and time-consuming to measure these interactions 

experimentally,” Baudry said. “But with 

supercomputers, we can process millions of molecules a day.”

The quick and efficient processing of 

molecules offers scientists an opportunity to take risks on previously unexamined drug candidates, which could 

lead to diverse and innovative classes 

of drugs.

“Before, we threw away a lot of information because molecules did not 

have a preferred profile,” Baudry said. 

“Now, every molecule can be examined 

without worrying about wasting resources.”

The researchers have already started 

work to launch the research into reality through a new collaboration supported by the National Institutes of 

Health. The project team plans to put 

the computational development to 

work on ORNL supercomputers to look 

for chemicals that could treat prostate cancer. The research is funded by 

a NIH Clinical Translational Science 

Award, which was awarded to Georgetown and Howard Universities and 

includes ORNL, Med/Star Health and 

the Washington D.C. Veterans Affairs 

Medical Center as key partners.

“Our development work is the computational equivalent of building the 

Saturn V rocket,” Baudry said. “Now we 

want to fly it to the moon.”

Funding for the initial development 

work was provided by ORNL’s Laboratory Directed Research and Development program. The University of 

Tennessee and the Joint UT/ORNL

Genome Sciences and Technology 

graduate program also supported the 

work. The research team included 

Barbara Collignon, Roland Schulz and 

Jeremy Smith of the UT-ORNL Center 

for Molecular Biophysics. The three 

researchers as well as Baudry are also 

affiliated with the University of Tennessee’s Department of Biochemistry 

and Cellular and Molecular Biology.

27
Understanding enzyme catalysis is an important part of our work, with two 

principal investigators, Hong Guo and Jerry Parks specializing in this field. Enzymes accelerate chemical reactions that are of critical importance in bioenergy, such as the hydrolysis of cellulose, and subsurface biogeochemistry, such 

as mercury detoxification. Although enzymologists can find out much useful 

information experimentally, only computer simulation, and, in particular quantum chemistry, can determine complete reaction mechanisms, producing ‘molecular movies’ of reactions happening with the corresponding energetics.

Hong Guo has a general interest 

in understanding the origin of the 

high catalytic efficiency and selectivity of enzymes. In addition 

to being of fundamental scientific 

importance, these studies also 

improve the basis for designing 

inhibitors, efficient drugs and enzyme mimics. He normally studies 

several systems at once, including recent work on protein lysine 

methyltransferases, RNA polymerases, serine-carboxyl peptidases, 

chorismate mutase, cytidine deaminase, and adenosine deaminase. 

He has also participated in DOE

work understanding the mechanism of action of a mercuric reductase and cellulases.

Jerry Parks came to CMB from the 

renowned group of Weitao Yang at 

Duke University, and is now spearheading research into catalysis involving mercury. Here, he discusses 

recent achievements and methodological roadblocks facing mixed 

quantum mechanical/molecular 

mechanical (QM/MM) methods.

Enzyme Catalysis

Faster Please

28
Quantum mechanical description of organomerucrial protonolysis. Two cysteine side chains in the active site of 

MerB coordinate with methylmercury, weakening the Hg-C bond. An aspartic acid side chain then protonates 

the -CH3

 leaving group, breaking the bond and forming Hg(II) and methane. 

What is the challenge of QM/MM 

calculations? Is it the accuracy? 

Is it the many possible reactions 

that need to be considered?

Parks: The issue is that there’s not just 

one challenge — there are several. For 

example, there’s always a trade-off 

between accuracy and affordability of 

the calculations. A given method needs 

to be assessed carefully to make sure 

it’s accurate enough for the questions 

you’re trying to address. There are 

often many potential reaction pathways that need to be considered, and 

it is important not to introduce bias 

when selecting reaction coordinates. 

Describing the electrostatic effects 

correctly right can be a challenge, and 

achieving converged statistical sampling isn’t easy either. The simulations 

are not simple. It’s really a bit of an 

art to do things correctly, and we’re 

definitely still learning. Also, you don’t 

always need to use QM/MM calculations. You can greatly simplify your life 

sometimes by just using a QM-only 

approach.

What characteristics of mercury catalysis have you learned 

from your calculations?

Parks: Using a QM-only active site 

model of the enzyme MerB, we learned 

how the enzyme breaks mercurycarbon bonds in methylmercury. 

Two cysteine side chains coordinate 

very strongly with methylmercury, 

which makes the mercury-carbon 

bond a bit longer and weaker. Then, 

a nearby aspartic acid side chain delivers a proton to the carbon atom. 

The result is that the enzyme produces inorganic Hg(II) and methane, 

and gets rid of methylmercury.

29
The simultaneous representation 

of biological processes at different length- and time-scales is a 

fervent area of research at present, 

and comes from the realization that 

coarse-graining of atomistic interactions is necessary to allow the simulation of processes at the cellular, and 

eventually organismal level. We are 

particularly interested in developing 

multiscale concepts that will be able 

to be used on petascale and exascale 

capability supercomputers. Work 

in this area spearheaded by Xiaolin 

Cheng has involved finding ways to 

treat solvent implicitly, rather than 

explicitly, using “treecode” electrostatics. Cheng, together with graduate student Xiaohu Hu has developed 

an Adaptive Fast Multipole PoissonBoltzmann (AFMPB) solver for the 

linearized Poisson-Boltzmann (LPB) 

equation, achieving an overall order 

N complexity for both computational 

speed and memory usage. The parallel version is still under development and will be optimized for running on DOE leadership computers.

Coarse graining work performed by 

postdoctoral fellow Goundla Srinivas 

and graduate student Dennis Glass, 

in collaboration with the Ames National Laboratory in Iowa, involves 

the development and application of 

Boltzmann inversion techniques and 

of the “REACH” (Realistic Extension 

Algorithm via Covariance Hessian) 

methodology developed by Kei Moritsugu of the RIKEN National Laboratory in Tokyo with Jeremy Smith, which 

maps results obtained from atomistic MD simulations onto models for 

larger-scale, coarse-grained MD. 

Applications of CMB multiscale methodology have been directed toward 

understanding plant cell-wall deconstruction. Hydrolysis of cell-wall cellulose is the critical, rate-limiting step 

in cellulosic biofuel production. The 

physical properties of lignocellulosic 

biomass thus derived serve as a basis 

for interpreting an array of biophysical experiments, and, in particular, 

the simulation models derived will 

be used to calculate and interpret a 

variety of neutron-scattering properties. This combination of simulation 

and experiment will eventually lead 

to a description of the physicochemical mechanisms of biomass recalcitrance to hydrolysis, and thus will aid 

in developing a strategy as to how 

rationally to overcome the resistance. 

Multiscale Methods

SCALING FROM ATOMS UPWARDS
Dynamical fingerprints, calculated from discrete states obtained from high-performance simulation, permit 

spectra to be calculated that can be directly compared with equivalent experimentally derived quantities.

Dynamical Fingerprints

There is a gap between kinetic experiments and simulations in their views 

of the dynamics of complex biomolecular systems. CMB in collaboration 

with Frank Noé of the Freie Universität 

Berlin, have presented a theoretical 

framework that reconciles these two 

approaches. “Dynamical fingerprints” 

contain peaks at the time scales of the 

dynamical processes that are involved 

with amplitudes determined by the 

experimental observable. Fingerprints 

can be generated from both experimental and simulation data, and their 

comparison by matching peaks permits assignment of structural changes 

present in the simulation to experimentally observed relaxation processes. This approach allows simulations to 

add a layer of complexity and realism 

to the interpretation of experiments 

such as neutron scattering. 

31
Row

Chain

... i+1 i i-1...

< non-reducing end reducing end >

1

2

3

...

M

Hydrogen Bond 

Networks in Cellulose

A major cause of biomass recalcitrance 

to deconstruction is the high structural 

ordering of natural cellulose fibrils, 

which arises largely from an extensive 

hydrogen-bond network between and 

within the cellulose polymers. Tongye 

Shen, Xiaolin Cheng and Jeremy Smith 

have worked with Heinrich Klein, an 

undergraduate student at the University of Heidelberg, to derive a latticebased model of hydrogen bonding 

in cellulose Iα. The plasticity of the 

hydrogen bond network as evidenced 

by two competing hydrogen bond 

patterns leads to an entropic contribution stabilizing the crystalline fibril at 

intermediate temperatures. At these 

temperatures, an enhanced probability 

of hydrogen bonding causes increased 

resistance of the entire fibril to deconstruction, before the final disassembly 

temperature is reached. The results 

thus provide a microscopic explanation for the physical origin of recalcitrance arising from the frustration of 

the hydrogen bond network.

An illustration of the sheet structure of cellulose Iα and the hydrogen bond network.

32
Coarse-Graining Cellulose

A systematic method has been developed by postdoctoral researcher 

Goundla Srinivas for generating and 

representing both crystalline and 

amorphous cellulose states. The developed CG models allow the exploration 

of cellulose fibril structures for lengthand time-scales beyond the reach of 

atomistic simulations. Srinivas has 

also been developing a CG force-field 

for cellulose fibrils in explicit water.

Transition of cellulose fibril from crystalline to amorphous structures.

33

Poplar: a potential biofuel feedstock investigated at ORNL.
How does a physicist survive in 

a biology department?

Shen: That is a tough question, and 

I am still figuring it out. You need so 

many things to be just right, such as 

luck and curiosity, and to ask the correct type of question that a physicist 

can answer. Physics always focuses on 

pure, ideal, and neat problems, while 

biological systems are much more 

complex. You can ask a lot of questions 

in biology and get a thousand different answers, but you don’t know which 

one is correct.

How does one overcome the inevitable communications problems that must exist between 

biologists and physicists?

Shen: I don’t see this as a huge problem. You just have to be open-minded, 

patient, and find common ground by 

using simple terms to explain what 

you mean. It is very rewarding to learn 

from for researchers from other fields 

and everybody is intrinsically curious.

Many experts think that the 

most innovative research is that 

which crosses disciplines. Why 

do you think this is so?

Shen: Not sure. But, assuming that 

each field has 10 good and trendy ideas, 

three fields may have 20 good ideas. If 

you cross several fields, you may be familiar with a lot more ideas than if you 

only know what is going on in your 

field alone. And of course 20 ideas can 

be a lot better than 10 ideas in solving a 

particular problem.

Tell us about your research on 

cellulose.

Shen: We are currently focused on 

understanding the structural stability 

of different phases of cellulose. I am 

surprised that not a lot more physical 

science researchers study this – it is 

really a very interesting problem. Just 

like ice having multiple phases due to 

extensive hydrogen bonding possibilities, polysaccharides also have a lot of 

bonding opportunities intramolecuHow does a Physicist Survive 

in a Biology Department?

Tongye Shen is an Assistant Professor 

in the UT Department of Biochemistry, 

Cellular and Molecular Biology. However, he looks at biological phenomena from a very physical standpoint, 

and his training differs substantially 

from that of most other faculty in the 

department.

34
larly and with their neighbors. Cellulose has many polymorphs as a result. 

To figure out how cellulose can transform from one form to another is very 

interesting. Postdoctoral researcher 

Xianghong “Hanna” Qi, a physicist and 

self-proclaimed expert on everything 

(Editorial note: said with a big grin), 

uses statistical physics to study this 

problem. We also examine the stochastic dynamics of the cellulose degradation by enzymes. This system is an 

excellent bridge to many other biological problems.

Why are lectins interesting and 

what have you discovered about 

them?

Shen: My early work was 100% on 

proteins, and then I moved on to study 

polysaccharides such as cellulose. So 

lectins are kind of a natural follow-up. 

Lectins have a bit of both, how proteins 

interact with sugar. With postdoctoral 

fellow Ricky Nellas, who is a chemist, 

and expert on nucleation theory, we 

are starting to look at how proteins effectively recognize sugars. This work is 

of importance in biology. In particular, 

we look at the cooperativity of proteinsugar recognition. That is, often lectins have multiple binding sites. This 

common feature indicates a certain 

enhancement of signaling. Cooperative binding will give an amplification 

effect on recognition.

You are adept at analytical physical theory. Are you working on 

applying analytical techniques 

to understanding biological systems at the moment? 

Shen: I like analytical models, probably 

because my first study area was the 

quantum mechanics of the excitation 

of heavy elements. For biological systems, analytical models can be tough 

for many reasons and I don’t particularly want to force it. I focus on the 

physical results and often have to settle 

for numerical results. Right now, we do 

have some very small analytical models: one for active assembly of swimming cells, another for the degradation 

of biopolymer chains. More often one 

cannot find many analytically solvable 

problems in biology, but more likely 

there is a specific condition of a system preventing solution. But analysis 

can nevertheless be useful in several 

ways. For example, say we use simulation/numerical methods to study F(x), 

with x in [0, 1]. Now we cannot solve it 

generally, but if we use an independent 

analytical method to get the solution at 

the end points, of F(0) and F(1), at least 

we get a sense of whether our numerical results are correct, and at those limiting cases, of what is happening.

35
ORNL over the Decades

CMB functions smoothly due in large 

part to Julia Cooper, our Administrative Assistant. Julia has been at ORNL 

for quite a while, and we found it interesting to hear her thoughts on life 

at the lab in earlier times.

Past years at ORNL were very different 

from the present. Union Carbide had 

the contract from the late 1940s until 

1984. Other contractors before UTBattelle were Lockheed Martin and 

Martin Marietta.

Before September 2001, Bethel Valley 

Road was open to all cars without 

restriction and there were no guard 

gates at either end as there are now. 

There was an approximately 10-foot 

fence with barbed wire on the top 

around the entire perimeter of the 

laboratory and guards were at each 

main entrance only for certain hours 

of the day, usually during regular 

working hours. Cars were required 

to be backed into the angled parking 

space – no pulling forward into it. 

The management structure was 

much different. There were Group 

Leaders, Section Heads and Division 

Directors for each division. Section 

heads did general supervision while 

division directors got the programs 

from DOE. There were more big 

programs in those days like Coal 

Conversion, and the Biology Division 

was internationally known for their 

genetics work. The big programs drew 

together a cross-section of expertise 

from across the whole lab. We had 

more immediate presence of the craft 

people, but also more support for the 

experimental scientists in the form 

of technicians. There are probably 

fewer technicians now since benchtype science has been replaced with 

more computer-based research.

People with seniority were generally 

Julia Cooper

Nurses sitting around a table with starched 

white uniforms

36
left alone to do their work, but there 

also was perhaps less openness. 

Safety has always been emphasized, 

but was not as micro-managed in 

years past. The complexity of lab 

regulations has grown considerably, 

which in some ways made things 

easier administratively. We didn’t use 

computers in the same ways we do 

now.

Women were regarded very differently 

in those days – there was less equality. 

The lab even had a “Miss ORNL” at 

some point – possibly in the early 60s! 

I’m not sure how she was chosen or 

the years this took place. Also, life in 

general was more formal. Both men 

and women wore more “dress” clothes 

to work – women often wore heels and 

men typically wore coats and ties. Very 

few wore jeans or casual attire. The 

nurses in medical wore starched white 

uniforms – all provided by ORNL! 

Bethel valley before ORNL

The old ORNL visitors center, with cars 

parked, presciently, “en battelle”.

37
Five Germans in Tennessee

When Jeremy Smith left Heidelberg to come to Tennessee in 2006 he managed 

to persuade five German students to follow him and register for a Ph.D. at UT. All 

five have now spent several years in East Tennessee and feel they even have a slight 

Southern accent to their English. We asked them to compare life in Knoxville to that 

in the rarified academia of Germany’s oldest university.

How’s life in Tennessee? 

Barmak: Pretty laid-back. I have to 

say my time here has helped me to 

become much more relaxed about 

many things in life. 

Benjamin: I like it. Being able to go 

shopping at 3 a.m. really fits the life 

of a scientist. Cars are essential – 

something you have to get used to 

– especially if you come from Europe, 

where public transit is very popular.

Dennis: It’s different in many small 

aspects, for example, the status of 

university sports, which are fun to 

discover.

Coming from far far away (left to right):

Barmak Mostofian, Benjamin Lindner, Dennis Glass, Roland Schulz, Xiaohu Hu

38
Roland: I like it. The nature is beautiful 

and the people are very nice. The main 

thing I don’t like is the urban sprawl.

Xiaohu: Nice warm weather – life is 

less hectic in general, nice people... 

and great BBQ! Oh my God is that 

good!

How would you compare the 

atmosphere at UT compared to 

the University of Heidelberg?

Dennis: I think undergraduate 

students in Heidelberg need to be 

more autonomous in planning 

their degree and workload, as the 

German system is quite flexible and 

formally wants students to get a broad 

education. Here, students benefit from 

well-designed degree paths and thus 

can give science a larger focus. 

Benjamin: The differences are very 

subtle. Both are gigantic institutes 

where the quality of the classes can 

vary significantly. A main difference is 

the timing of the semesters. UT allows 

you to enjoy Christmas because the fall 

semester ends before Christmas takes 

place.

Barmak: There are cultural differences 

as well. I think the University of 

Heidelberg has one of the largest 

medical centers in Germany while 

Knoxville has one of the largest football 

stadiums in the U.S. They name their 

department buildings after famous 

scientists in Heidelberg, while in 

Tennessee they are named after 

famous football players.

Xiaohu: In Heidelberg, we didn’t care 

much about University sports events, 

but here everybody is crazy about UT’s 

football team. It was quite an amazing 

phenomenon for me at the beginning.

Roland: In Heidelberg the learning 

process is less structured, e.g. 

attendance is often not required and 

for a PhD few classes are mandatory. 

UT offers more help with non-subject 

skill development such as grant 

writing.

Are the students the same?

Benjamin: At UT you see more 

international students. The students 

themselves are not that different. 

Roland: The German school system 

causes Heidelberg students to be on 

average a bit older but better prepared 

in Math.

Xiaohu: I’d say yes. People are working 

hard to get their degrees similar to 

Heidelberg.

Has Jeremy become a little 

less snobbish since leaving 

the German “Herr Professor” 

establishment?

Benjamin: I never had the feeling that 

Jeremy was snobbish. Otherwise I

wouldn’t be here. 

Dennis: I think Jeremy was always 

“Jeremy” and never “Herr Professor”, 

and he still is “Jeremy” in Tennessee. 

39
Roland: I think that the majority 

of professors in Germany are not 

snobbish. This included Jeremy when 

he was still there.

Xiaohu: “Herr Professor”? I don’t 

think these words have ever been in 

Jeremy’s vocabulary. Besides, these 

words would make our young and 

dynamic Jeremy sounds he was 75+ 

and driving a motorized wheelchair 

to work rather than a BMW M3 

convertible (Editorial note: it’s actually 

a 3-series convertible, not an M3), 

which is envied by all of us poor 

graduate students, but at the same 

time, also motivates us to work hard to 

become like Jeremy in the future. No, 

we have never called him anything 

else but Jeremy... Wait, what is his last 

name again? Jeremy Schmidt? :)

What’s the verdict on outdoor 

activities in Tennessee?

Barmak: Hiking, biking, climbing, 

rafting, canoeing, boating, camping 

– you name it! If it wasn’t for the 

Smokies, I’ve heard, we all would have 

been much more productive at work.

Benjamin: Not good for skiing though 

– also the climate can be tough 

sometimes. 

Dennis: You can go hiking and 

actually see wildlife, unlike in 

Germany where the only “wildlife” that 

will cross your way is mostly other 

hikers. Be aware if they just left a 

“Hütte“ that served alcoholic beverages, 

they might literally cross your way.

Roland: The large number of trails, 

both for hiking and mountain-biking, 

is very nice. In Heidelberg mountainbikers have to share trails with hikers 

and are hated by most of them. The 

Smokies are very beautiful. Particularly 

amazing are the synchronized fireflies.

Xiaohu: Well, there are some 

similarities between Heidelberg and 

Knoxville in this aspect: near Knoxville, 

there is the Great Smoky Mountains 

and near Heidelberg, there is the 

Odenwald (Oden-forest). Both are 

good for hiking, but I think there is 

clearly more wildlife in the Smokies. I

don’t think anyone has seen wild bears 

in the Odenwald before.

What’s the difference between 

science in Germany and the 

USA?

Benjamin: The leadership feeling. 

Great science takes place in both 

40

Liang Hong expresses an opinion to a hardworking visiting student from Heidelberg – 

Mai Zahran.
locations, but it’s like comparing 

the NBA with the German basketball 

league. Incidentally, a current NBA

superstar is German: Dirk Nowitzki. 

Dennis: I can just speak for the 

graduate student part of science – 

Here I prefer the German system 

where you start graduate school on 

a level similar to the Master’s degree, 

have no obligatory coursework, and 

can focus right on your research 

(instead of course-work).

Roland: The three difference I

find most striking are: 1) Scientific 

Computing receives more attention 

and funding than in Germany. E.g. 

51% of the TOP500 and 50% of the 

TOP10 of supercomputers are in the 

US versus 6% of TOP500 and 0% of 

TOP10 for Germany. The current plans 

in the US for Exascale computing are 

far ahead of plans in Germany. 2) The 

funding of research groups is much 

more reliant on external funding by 

research grants than it is in Germany; 

thus the importance of grant writing is 

much higher in the US. 3) For science 

education a striking difference is the 

acceptance of some scientific theories. 

Having volunteered for the UTK 

Darwin Day I have experienced some 

of the challenges evolution education 

faces in the US. Also climate science 

is much more political than it is in 

Germany whereas the opposite is true 

for food biotechnology and nuclear 

research.

Xiaohu: In principle, not really 

different, working hard and producing 

good publications.

Will Juergen Klinsmann 

succeed as coach of Soccer 

Team USA?

Barmak: Haha, I guess he will be just 

fine. In fact, I would say if there is 

one team that would not lose against 

Germany in the 2014 World Cup, it will 

be Team USA.

Benjamin - You were a topclass wrestler back in Germany, 

and even competed for the 

national team. Does the US 

pull its weight in international 

wrestling?

Benjamin: As a matter of fact I don’t 

know. Even though I was a successful 

wrestler I never really cared about the 

who’s who in wrestling. I wrestled 

because that is what I loved to do. Now 

it’s computational science.

Which is the liveliest: the 

Cumberland Strip or the 

Heidelberg Hauptstraße?

Dennis: Heidelberg what? I’ve been 

here for a while and hardly remember 

a previous life... 

Jeremy infinitely prefers 

bluegrass music to German 

“Volksmusik”. Do you agree?

Xiaohu: Oh yes, definitely! Compared 

to other music, Volksmusik is not 

nearly as enjoyable as is a Volkswagen 

compared to other automobiles.

41
Question: What sparked your interest 

to pursue a career in science?

Jeremy Smith: In England in the 1970s 

one had to specialize early, very early 

-- at 16. For me it could have gone either 

way, arts or sciences. To be honest I

wasn’t very interested in science at that 

time. I was never a geeky, gadget-type 

kid, although scientific concepts did 

interest me. My high school teachers 

advised science as having safer career 

prospects than arts subjects, so from 17 

on that’s all I did. Later in high school I

became interested in protein structures 

and how atoms interact. I sometimes 

wonder what would have happened if 

I’d chosen the other way at 16...

Q: As the Director of the Center for 

Molecular Biophysics, your work spans 

across a multitude of fields. Can you 

tell us a little about your research background -- what led you to this unique 

position?

JS: My first degree was in biophysics at 

Leeds, England. After that, I did a Ph.D. 

in neutron scattering in France, a post 

doc in chemistry at Harvard, and then 

ran my first group at the French National Lab in Saclay. Before coming to 

Tennessee I held the Chair of Computational Molecular Biophysics at the University of Heidelberg in Germany. Yes, 

our work involves theoretical physics, 

quantum chemistry, statistical mechanics, computer science, supercomputing, 

catalytic chemistry, polymer science, 

biochemistry, molecular biology -- you 

name it!

I find it difficult to not get enthusiastic 

about a crisp new idea in molecular science and how we might help develop it.

Q: What projects are you working on 

right now? What do you hope they will 

lead to?

JS: We’re working on many different 

projects. Some of these include: cellulosic biofuels, which we hope will lead to 

cheap alternative energy, drug discovery towards curing prostate cancer and 

mercury biogeochemistry to understand 

the fate of mercury in the environment. 

We’re also working on describing the 

structure and dynamics of biological 

materials through neutron scattering. 

With regards to supercomputing, those 

The article below was posted on the energy blog of the Department of Energy.

10 Questions for a Biophysicist: 

Jeremy Smith

Source: http://energy.gov/articles/10-questions-biophysicist-jeremy-smith

In 2006, Dr. Smith came to Oak Ridge National Laboratory (ORNL). Since then, he 

has led a wide-ranging spectrum of projects focusing on everything from biofuels to 

drug discovery. He recently gave us the download on his many projects.

Dr Jeremy Smith | Photo Courtesy of ORNL

42
cheeky hardware guys keep building 

more and more powerful machines and 

challenging us to perform cutting-edge 

simulations that efficiently use their full 

capability.

Q: You are also a professor at University 

of Tennessee -- do you have any advice 

for students interested in science?

JS: Yes. Learn to write well -- too many 

youngsters can do science but not precisely express their thoughts and findings. Furthermore, don’t forget to lead 

a balanced, active, fun life -- it will help 

the scientific part.

Q: What classes do you teach? What 

have your students taught you?

JS: I teach an introduction to molecular 

biophysics, a journal club and our group 

meetings. My co-workers and students 

come up with all the crazy ideas and 

then do all the work -- they’re sickeningly bright and inexhaustibly hardworking.

Q: What can you never start a day at the 

lab without?

JS: I like to start the day finding a new 

research manuscript on my desk that 

a co-worker has left for me, preferably 

with a cookie on top.

Q: Do you have a favorite fictional scientist?

JS: Yes, Gromit. He remembered to take 

the handbrake off his rocket.

Q: We heard that you are an avid soccer fan and player -- having lived in 

England, France, Germany and now the 

United States, do you have a favorite for 

the next World Cup?

JS: Concerning playing soccer -- my 

79-year-old father still plays ninety 

minute games so I can’t possibly give up 

playing until he does, can I?

I’m the equivalent of a Cubs fan. I support Norwich City, a team in England 

apparently consigned to perennial failure, except of course, maybe, this year 

(hope springs eternal)! As for the World 

Cup, supporting England is too painful so I’ll just say anyone but Germany, 

please.

Q: What is it like to work in ORNL’s 

Spallation Neutron Source (SNS) facility?

JS: Well, the SNS brings together scientists from many different fields. It’s 

sometimes difficult for me to understand what someone from, for example, 

magnetism is working on but the diversity of backgrounds leads to fertile 

discussion. It will take a while before 

SNS achieves full science productivity 

and then a couple more years until the 

results obtained have their full effects 

on the scientific community but we’re 

getting there.

Q: Last question -- why is neutron scattering research important?

JS: Neutrons give direct, simultaneous 

information on molecular structure and 

dynamics and no other probe of matter does this. This should help us design 

new materials in the energy sciences, 

and understand important topics in bioenergy and biology. For example, we recently demonstrated with neutrons how 

a cancer drug, methotrexate, softens the 

target it binds to -- that’s fundamental 

understanding of how drugs work.

43
CMB Publications

2006 (October onwards)

Baudry J (2006) Van der Waals Interactions and Decrease of the Rotational Barrier of Methyl-size Rotators: A

Theoretical Study. Journal of the American Chemical Society 128(34):11088-11093.

Efferth T, Schwarzl SM, Smith JC & Osieka R (2006) Role of Glucose-6-Phosphate Dehydrogenase for Oxidative Stress and Apoptosis. Cell Death and Differentiation 13:527-528.

Guo H, Wlodawer A, Nakayama T, Xu Q & Guo H (2006) Catalytic Role of Proton Transfers in the Formation of 

a Tetrahedral Adduct in a Serine Carboxyl Peptidase. Biochemistry 45(30):9129--9137.

Koppole S, Smith JC & Fischer S (2006) Simulations of the Myosin II Motor Reveal a Nucleotide-State Sensing 

Element that Controls the Recovery Stroke. Journal of Molecular Biology 361(3):604-616.

Kurkal-Siebert V & Smith JC (2006) Low-Temperature Protein Physics: A Simulation Analysis of Interprotein 

Vibrations and the Boson Peak at 150K. Journal of the American Chemical Society 128(7):2356-2364.

Moritsugu K & Smith JC (2006) Temperature-Dependent Protein Dynamics: A Simulation-Based Probabilistic Diffusion-Vibration Langevin Description. The Journal of Physical Chemistry B 110(11):5807-5816.

Noé F, Krachtus D, Smith JC & Fischer S (2006) Transition Networks for the Comprehensive Characterization 

of Complex Conformational Change in Proteins. Journal of Chemical Theory and Computation 2(3):840-857.

Noé F, Oswald M, Reinelt G, Fischer S & Smith JC (2006) Computing Best Transition Pathways in High-Dimensional Dynamical Systems. Journal of Multiscale Modelling and Simulation 5(2):393-419.

Smith JC (2006) Tight in Titin. Structure 14(3):389-390.

Tehei M, Smith JC, Monk C, Ollivier J, Öttl M, Kurkal V, Finney JL & Daniel RM (2006) Dynamics of Immobilized and Native Escherichia coli Dihydrofolate Reductase by Quasieleastic Neutron Scattering. Biophysical 

Journal 90(3):1090-1097.

Xu Q, Guo H-B, Wlodawer A & Guo H (2006) The Importance of Dynamics in Substrate-Assisted Catalysis 

and Specificity. Journal of the American Chemical Society 128(18):5994--5995.

2007

Bondar A-N, Suhai S, Fischer S, Smith JC & Elstner M (2007) Suppression of the Back Proton-Transfer from 

Asp85 to the Retinal Schiff Base in Bacteriorhodopsin: A Theoretical Analysis of Structural Elements. Journal 

of Structural Biology 157(3):454-469. 

Bondar A-N, Suhai S, Smith JC & Frangopol PT (2007) Computer Simulations of Local Anesthetic Mechanisms: Quantum Chemical Investigation of Procaine. Romanian Reports in Physics 59(2):289-299.

Cournia Z, Ullmann MG & Smith JC (2007) Differential Effects of Cholesterol, Ergosterol and Lanosterol on a 

Dipalmitoyl Phosphatidylcholine Membrane: A Molecular Dynamics Simulation Study. Journal of Physical 

Chemistry B 111(7):1786-1801.

Daidone I, Ulmschneider MB, Di Nola A, Amadei A & Smith JC (2007) Dehydration-Driven Solvent Exposure 

of Hydrophobic Surfaces as a Driving Force in Peptide Folding. Proceedings of the National Academy of Sciences (U.S.A.) 104(39):15230-15235.

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de Hatten X, Cournia Z, Huc I, Smith JC & Metzler-Nolte N (2007) Force-Field Development and Molecular 

Dynamics Simulations of Ferrocene-Peptide Conjugates as a Scaffold for Hydrogenase Mimics. Chemistry - 

A European Journal 13(29):8139-8152.

Guo H-B & Guo H (2007) Mechanism of Histone Methylation Catalyzed by Protein Lysine Methyltransferase SET7/9 and Origin of Product Specificity. Proceedings of the National Academy of Sciences (U.S.A.)

104(21):8797-8802.

Koppole S, Smith JC & Fischer S (2007) The Structural Coupling between ATPase Activation and Recovery 

Stroke in the Myosin II Motor. Structure 15(7):825--837.

Meinhold L, Merzel F & Smith JC (2007) Lattice Dynamics of a Protein Crystal. Physical Review Letters

99(13):138101.

Meinhold L & Smith JC (2007) Protein Dynamics from X-Ray Crystallography: Anisotropic, Global Motion in 

Diffuse Scattering Patterns. Proteins 66(4):941-953.

Meinhold L, Smith JC, Kitao A & Zewail AH (2007) Picosecond Fluctuating Protein Energy Landscape 

Mapped by Pressure Temperature Molecular Dynamics Simulation. Proceedings of the National Academy of 

Sciences (U.S.A.) 104(44):17261-17265.

Mesentean S, Koppole S, Smith JC & Fischer S (2007) The Principal Motions Involved in the Coupling Mechanism of the Recovery Stroke of the Myosin Motor. Journal of Molecular Biology 367(2):591-602.

Moritsugu K & Smith JC (2007) Coarse-Grained Biomolecular Simulation with REACH: Realistic Extension 

Algorithm via Covariance Hessian. Biophysical Journal 93(10):3460-3469.

Noé F, Horenko I, Schütte C & Smith JC (2007) Hierarchical Analysis of Conformational Dynamics in Biomolecules: Transition Networks of Metastable States. Journal of Chemical Physics 126(15):155102.

Nutt DR & Smith JC (2007) Choosing an Appropriate Water Model for Use in Biomolecular Simulations in 

Physics and Chemistry of Ice, ed Kuhs WF (RSC Publishing), pp 451-458.

Nutt DR & Smith JC (2007) Molecular Dynamics Simulations of Proteins: Can the Explicit Water Model Be 

Varied? Journal of Chemical Theory and Computation 3(4):1550-1560.

Topham CM & Smith JC (2007) Orientation Preferences of Backbone Secondary Amide Functional Groups in 

Peptide Nucleic Acid Complexes: Quantum Chemical Calculations Reveal an Intrinsic Preference of Cationic 

D-Amino Acid-Based Chiral PNA Analogues for the P-form. Biophysical Journal 92(3):769-786.

Xu Q, Guo H-B, Gorin A & Guo H (2007) Stabilization of a Transition-State Analogue at the Active Site of Yeast 

Cytosine Deaminase: Importance of Proton Transfers. Journal of Physical Chemistry B 111(23):6501-6506.

Xu Q, Guo H-B, Wlodawer A, Nakayama T & Guo H (2007) The QM/MM Molecular Dynamics and Free Energy 

Simulations of the Acylation Reaction Catalyzed by the Serine-Carboxyl Peptidase Kumamolisin-As. Biochemistry 46(12):3784-3792.

2008

Becker V, Sengupta D, Ketteler R, Ullmann MG, Smith JC & Klingmüller U (2008) Packing Density of the 

Erythropoietin Receptor Transmembrane Domain Correlates with Amplification of Biological Responses. 

Biochemistry 47(45):11771-11782.

Bondar A-N, Baudry J, Suhai S, Fischer S & Smith JC (2008) Key Role of Active-Site Water Molecules in Bacteriorhodopsin Proton-Transfer Reactions. Journal of Physical Chemistry B 112(47):14729-14741.

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Krishnan M, Kurkal-Siebert V & Smith JC (2008) Methyl Group Dynamics and the Onset of Anharmonicity in 

Myoglobin. Journal of Physical Chemistry B 112(17):5522-5533.

Kurkal-Siebert V, Agarwal R & Smith JC (2008) Hydration-Dependent Dynamical Transition in Protein: Protein Interactions at Approximately 240 K. Physical Review Letters 100(13):138102.

McLain SE, Soper AK, Daidone I, Smith JC & Watts A (2008) Charge-Based Interactions between Peptides 

Observed as the Dominant Force for Association in Aqueous Solution. Angewandte Chemie International 

Edition 120(47):9199-9202.

Meinhold L, Clement D, Tehei M, Daniel R, Finney JL & Smith JC (2008) Protein Dynamics and Stability: The 

Distribution of Atomic Fluctuations in Thermophilic and Mesophilic Dihydrofolate Reductase Derived Using 

Elastic Incoherent Neutron Scattering. Biophysical Journal 94(12):4812--4818.

Moritsugu K & Smith JC (2008) REACH Coarse-Grained Biomolecular Simulation: Transferability between 

Different Protein Structural Classes. Biophysical Journal 95(4):1639--1648.

Neusius T, Daidone I, Sokolov IM & Smith JC (2008) Subdiffusion in Peptides Originates from the FractalLike Structure of Configuration Space. Physical Review Letters 100(18):188103.

Noé F, Daidone I, Smith JC, Di Nola A & Amadei A (2008) Solvent Electrostriction-Driven Peptide Folding Revealed by Quasi-Gaussian Entropy Theory and Molecular Dynamics Simulation. Journal of Physical Chemistry B 112(35):11155-11163.

Nutt DR & Smith JC (2008) Dual Function of the Hydration Layer around an Antifreeze Protein Revealed by 

Atomistic Molecular Dynamics Simulations. Journal of the American Chemical Society 130(39):13066-13073.

Petridis L & Smith JC (2008) Cellulosic Ethanol: Progress towards a Simulation Model of Lignocellulosic Biomass. Journal of Physics: Conference Series 125(1):012055.

Sengupta D, Smith JC & Ullmann GM (2008) Partitioning of Amino-Acid Analogues in a Five-Slab Membrane Model. Biochimica et Biophysica Acta 1778(10):2234--2243.

Voltz K, Trylska J, Tozzini V, Kurkal-Siebert V, Langowski J & Smith JC (2008) Coarse-Grained Force Field for 

the Nucleosome from Self-Consistent Multiscaling. Journal of Computational Chemistry 29(9):1429-1439.

2009

Bondar A-N & Smith JC (2009) Water Molecules in Short- and Long-Distance Proton Transfer Steps of Bacteriorhodopsin Proton Pumping. Israel Journal of Chemistry 49(2):155-161.

Cheng X, Ivanov I, Wang HL, Sine SM & McCammon JA (2009) Molecular-Dynamics Simulations of ELIC - a 

Prokaryotic Homologue of the Nicotinic Acetylcholine Receptor. Biophysical Journal 96(11):4502-4513.

Guo H-B, Gorin A & Guo H (2009) A Peptide-Linkage Deletion Procedure for Estimate of Energetic Contributions of Individual Peptide Groups in a Complex Environment: Application to Parallel β-Sheets. Interdisciplinary Sciences: Computational Life Sciences 1(1):12--20.

Imhof P, Fischer S & Smith JC (2009) Catalytic Mechanism of DNA Backbone Cleavage by the Restriction 

Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical Analysis. Biochemistry 48(38):9061-9075.

Krishnan M, Schulz R & Smith JC (2009) Protein Dynamical Transition: Role of Methyl Dynamics and Local Diffusion. Theory and Applications of Computational Chemistry 2008. AIP Conference Proceedings

1102:122-131.

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Krishnan M & Smith JC (2009) Response of Small-Scale, Methyl Rotors to Protein-Ligand Association: A Simulation Analysis of Calmodulin-Peptide Binding. Journal of the American Chemical Society 131(29):10083-

10091.

Moritsugu K, Kurkal-Siebert V & Smith JC (2009) REACH Coarse-Grained Normal Mode Analysis of Protein 

Dimer Interaction Dynamics. Biophyical Journal 97(4):1158-1167.

Moritsugu K & Smith JC (2009) REACH: A Program for Coarse-Grained Biomolecular Simulation. Computer 

Physics Communications 180(7):1188-1195.

Neusius T, Sokolov IM & Smith JC (2009) Subdiffusion in Time-Averaged, Confined Random Walks. Physical 

Review E 80:011109.

Parks JM, Guo H, Momany C, Liang L, Miller SM, Summers AO & Smith JC (2009) Mechanism of Hg-C Protonolysis in the Organomercurial Lyase MerB. Journal of the American Chemical Society 131(37):13278-13285.

Petridis L & Smith JC (2009) A Molecular Mechanics Force Field for Lignin. Journal of Computational Chemistry 30(3):457-467.

Phatak P, Fraemcke JS, Wanko M, Hoffmann M, Strodel P, Smith JC, Suhai S, Bondar AN & Elstner M (2009) 

Long-Distance Proton Transfer with a Break in the Bacteriorhodopsin Active Site. Journal of the American 

Chemical Society 131(20):7064-7078.

Schulz R, Krishnan M, Daidone I & Smith JC (2009) Instantaneous Normal Modes and the Protein Glass 

Transition. Biophysical Journal 96(2):476-484.

Schulz R, Lindner B, Petridis L & Smith JC (2009) Scaling of Multimillion-Atom Biological Molecular Dynamics Simulation on a Petascale Supercomputer. Journal of Chemical Theory and Computation 5(10):2798-2808.

Shen T, Langan P, French A, Johnson GP & Gnanakaran S (2009) Conformational Flexibility of Soluble Cellulose Oligomers: Chain Length and Temperature Dependence. Journal of the American Chemical Society

131(41):14786-14794.

Smith JC (2009) Supercomputers Tackle Biofuel Production Problems. SciDAC Review (15):34-45.

Spies A, Reese JG, Dodd D, Pankow KL, Blanke SR & Baudry J (2009) Determinants of Catalytic Power and 

Ligand Binding in Glutamate Racemase. Journal of the American Chemical Society 131(14):5274-5284.

Splettstoesser T, Noé F, Oda T & Smith JC (2009) Nucleotide-Dependence of G-Actin Conformation from 

Multiple Molecular Dynamics Simulations and Observation of a Putatively Polymerization-Competent Superclosed State. Proteins: Structure, Function, and Bioinformatics 76(2):353-364.

Thurkal L, Smith JC & Daidone I (2009) Common Folding Mechanism of a Beta-Hairpin Peptide via NonNative Turn Formation Revealed by Unbiased Molecular Dynamics Simulations. Journal of the American 

Chemical Society 131(50):18147-18152.

Ulmschneider JP, Smith JC, Killian A & Ulmschneider MB (2009) Peptide Partitioning and Folding into Lipid 

Bilayers. Journal of Chemical Theory and Computation 5(9):2202-2205.

Xu J, Crowley MF & Smith JC (2009) Building a Foundation for Structure-Based Cellulosome Design for Cellulosic Ethanol: Insight into Cohesin-Dockerin Complexation from Computer Simulation. Protein Science

18(5):949--959.

Xu Q, Chu Y, Guo H-B, Smith JC & Guo H (2009) Energy Triplets for Writing Epigenetic Marks: Insights from 

QM/MM Free Energy Simulations of Protein Lysine Methyltransferases. Chemistry: A European Journal

15(46):12596-12599.

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Xu Q, Ye X, Li L-Y, Cheng Z-M & Guo H (2009) Structural Basis for the Action of Xyloglucan Endotransglycosylases/hydrolases: Insights from Homology Modeling. Interdisciplinary Sciences: Computational Life Sciences 2(2):133-139.

2010

Bellesia G, Asztalos A, Shen T, Langan P, Redondo A & Gnanakaran S (2010) In Silico Studies of Crystalline 

Cellulose and Its Degradation by Enzymes. ACTA Crystallographica. Section D: Biological Crystallography

66(11):1184-1188.

Berezniak T, Zahran M, Imhof P, Jaeschke A & Smith JC (2010) Magnesium-Dependent Active-Site Conformational Selection in the Diels-Alderase Ribozyme. Journal of the American Chemical Society 132(36):12587-

12596.

Bondar A-N, Smith JC & Elstner M (2010) Mechanism of a Proton Pump Analyzed with Computer Simulations. Theoretical Chemistry Accounts 125(3-6):353-363.

Chu Y, Xu Q & Guo H (2010) Understanding Energetic Origins of Product Specificity of SET8 from QM/MM 

Free Energy Simulations: What Causes the Stop of Methyl Addition during Histone Lysine Methylation? 

Journal of Chemical Theory and Computation 6(4):1380-1389.

Daidone I, Neuweiler H, Doose S, Sauer M & Smith JC (2010) Hydrogen-Bond Driven Loop-Closure Kinetics 

in Unfolded Polypeptide Chains. PLoS Computational Biology 6(1):e1000645.

Glass D, Krishnan M, Nutt D & Smith JC (2010) Temperature Dependence of Protein Dynamics Simulated 

with Three Different Water Models. Journal of Chemical Theory and Computation 6(4):1390-1400.

Guan Y, Ranoa DRE, Jiang S, Mutha SK, Li X, Baudry J & Tapping RI (2010) Human TLRs 10 and 1 Share Common Mechanisms of Innate Immune Sensing but Not Signaling. The Journal of Immunology 184(9):5094-

5103.

Guo H-B, Johs A, Parks JM, Oliff L, Miller SM, Summers AO, Liang L & Smith JC (2010) Structure and Conformational Dynamics of the Metalloregulator MerR upon Binding of Hg(II). Journal of Molecular Biology

398(4):555-568.

Johnson Q, Doshi U, Shen T & Hamelberg D (2010) Water’s Contribution to the Energetic Roughness from 

Peptide Dynamics. Journal of Chemical Theory and Computation 6(9):2591-2597.

Lopez M, Kurkal-Siebert V, Dunn RV, Tehei M, Finney JL, Smith JC & Daniel RM (2010) Activity and Dynamics of an Enzyme, Pig Liver Esterase, in Near-Anhydrous Conditions. Biophysical Journal 99(8):L62-L64.

Lu B, Cheng X, Huang J & McCammon JA (2010) AFMPB: An Improved Poisson-Boltzmann Solver Using an 

Adaptive Fast Multipole Method. Computer Physics Communications 181(6):1150-1160.

Lynch RM, Rong R, Li B, Shen T, Honnen W, Mulenga J, Allen S, Pinter A, Gnanakaran S & Derdeyn CA (2010) 

Subtype-Specific Conservation of Isoleucine 309 in the Envelope V3 Domain is Linked to Immune Evasion 

in Subtype C HIV-1 Infection. Virology 404(1):59-70.

Moritsugu K, Njunda BM & Smith JC (2010) Theory and Normal Mode Analysis of Change in Protein Vibrational Dynamics on Ligand Binding. Journal of Physical Chemistry B 114(3):1479-1485.

Saharay M, Guo H & Smith JC (2010) Mechanism of Cellulose Degradation by a Cellobiohydrolase, CelS. PLos 

ONE 5(10):e12947.

Ulmschneider MB, Doux JPF, Killian JA, Smith JC & Ulmschneider JP (2010) Mechanism and Kinetics of 

Peptide Partitioning into Membranes from All-Atom Simulations of Thermostable Peptides. Journal of the 

American Chemical Society 132(10):3452-3460.

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Ulmschneider MB, Smith JC & Ulmschneider JP (2010) Peptide Partitioning Properties from Direct Insertion 

Studies. Biophysical Journal 98(12):L60-L62.

Xu J & Smith JC (2010) Probing the Mechanism of Cellulosome Attachment to the Clostridium thermocellum Cell Surface: Computer Simulation of the Type II Cohesin-Dockerin Complex and Its Variants. Protein 

Engineering, Design and Selection 23(10):759-768.

Xu Q, Li L & Guo H (2010) Understanding the Mechanism of Deacylation Reaction Catalyzed by the Serine 

Carboxyl Peptidase Kumamolisin-As: Insights from QM/MM Free Energy Simulations. The Journal of Physical Chemistry B 114(32):10594-10600.

Yang S, Land ML, Klingeman DM, Pelletier DA, Lu T-YS, Martin SL, Guo H-B, Smith JC & Brown SD (2010) A

Paradigm for Strain Improvement Identifies Sodium Acetate Tolerance Loci in Zymomonas mobilis and Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences (U.S.A.) 107(23):10395-10400.

Zahran M, Daidone I, Smith JC & Imhof P (2010) Mechanism of DNA Recognition by the Restriction Enzyme 

EcoRV. Journal of Molecular Biology 401(3):415-432.

2011

Balog E, Perahia D, Smith JC & Merzel F (2011) Vibrational Softening of a Protein on Ligand Binding. The 

Journal of Physical Chemistry B 115(21):6811-6817.

Bondar A-N, Fischer S & Smith JC (2011) Water Pathways in the Bacteriorhodopsin Proton Pump. Journal of 

Membrane Biology 239(1-2):73-84.

Brown SD, Guss AM, Karpinets TV, Parks JM, Smolin N, Yang S, Land ML, Klingeman DM, Bhandiwand A, 

Rodriguez M, Raman B, Shao X, Mielenz JR, Smith JC, Keller M & Lynd LR (2011) Mutant Alcohol Dehydrogenase Leads to Improved Ethanol Tolerance in Clostridium thermocellum. Proceedings of the National 

Academy of Sciences (U.S.A.) 108(33):13752-13757.

Collignon B, Schulz R, Smith JC & Baudry J (2011) Task-Parallel MPI Implementation of Autodock4 for Docking of Very Large Databases of Compounds Using High Performance Super-Computers. Journal of Computational Chemistry 32(6):1202-1209.

Daidone I, Di Nola A & Smith JC (2011) Molecular Origin of Gerstmann-Sträussler-Scheinker Syndrome: Insight from Computer Simulation of an Amyloidogenic Prion Peptide. Biophysical Journal 100(12):3000-3007.

Fritsch S, Ivanov I, Wang H & Cheng X (2011) Ion Selectivity Mechanism in a Bacterial Pentameric LigandGated Ion Channel. Biophysical Journal 100(2):390-398.

Hembree WI & Baudry J (2011) Three-dimensional Mapping of Micro-environmental Control of Methyl Rotational Barriers. Journal of Physical Chemistry B 115(26):8575-8580.

Li L, Jiang X, Guan H, Wang P & Guo H (2011) Three Alginate Lyases from Marine Bacterium Pseudomonas 

fluorescens HZJ216: Purification and Characterization. Applied Biochemistry and Biotechnology 164(3):305-

317.

Li T, Choi W-G, Wallace IS, Baudry J & Roberts DM (2011) Arabidopsis thaliana NIP7;1: An Anther-Specific 

Boric Acid Transporter of the Aquaporin Superfamily Regulated by an Unusual Tyrosine in Helix 2 of the 

Transport Pore. Biochemistry 50(31):6633-6641.

Neusius T, Daidone I, Sokolov I & Smith JC (2011) Configurational Subdiffusion of Peptides: A Network Study. 

Physical Review E 83:021902.

Noé F, Doose S, Daidone I, Lollmann M, Sauer M, Chodera JD & Smith JC (2011) Dynamical Fingerprints: 

Probing Individual Relaxation Processes in Biomolecular Dynamics with Simulations and Kinetic Experi81

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ments. Proceedings of the National Academy of Sciences (U.S.A) 108(12):4822-4827.

Petridis L, Xu J, Crowley M, Smith JC & Cheng X (2011) Self-Similar Multiscale Structure of Lignin Revealed 

by Neutron Scattering and Molecular Dynamics Simulation. Physical Review E 83:061911.

Petridis L, Xu J, Crowley M, Smith JC & Cheng X (2011) Atomistic Simulation of Lignocellulosic Biomass and 

Associated Cellulosomal Protein Complexes. Computational Modeling in Lignocellulosic Biofuel Production, 

eds Nimlos MR & Crowley MF (ACS Publications), Vol 1052, pp 55-73.

Philip V, Harris J, Adams R, Nguyen D, Spiers J, Baudry J, Howell EE & Hinde RJ (2011) A Survey of AspartatePhenylalanine and Glutamate-Phenylalanine Interactions in the Protein Data Bank: Searching for Anion-Π

Pairs. Biochemistry 50(14):2939-2950.

Pingali SV, O’Neill HM, McGaughey J, Urban VS, Rempe CS, Petridis L, Smith JC, Evans BR & Heller WT (2011) 

Small-Angle Neutron Scattering Reveals pH-Dependent Conformational Changes in Trichoderma reesei 

Cellobiohydrolase I: Implications for Enzymatic Activity. Journal of Biological Chemistry 286:32801-32809.

Prinz J-H, Chodera J, Pande V, Swope W, Smith JC & Noé F (2011) Optimal Use of Data in Parallel Tempering 

Simulations for the Construction of Discrete-State Markov Models of Biomolecular Dynamics. Journal of 

Chemical Physics 134:244108.

Saharay M, Guo H-B, Smith JC & Guo H (2011) QM/MM Analysis of Cellulase Active Sites and Actions of the 

Enzymes on Substrates. Computational Modeling in Lignocellulosic Biofuel Production, eds Nimlos MR & 

Crowley MF (ACS Publications), Vol 1052, pp 135-154.

Splettstoesser T, Holmes KC, Noé F & Smith JC (2011) Structural Modeling and Molecular Dynamics Simulation of the Actin Filament. Proteins: Structure, Function, and Bioinformatics 79(7):2033-2043.

Wang SS, Shen T & Wolynes PG (2011) The Interplay of Nonlinearity and Architecture in Equilibrium Cytoskeletal Mechanics. Journal of Chemical Physics 134(1):014510.

Xu Q, Yao J, Wlodawer A & Guo H (2011) Clarification of the Mechanism of Acylation Reaction and Origin of 

Substrate Specificity of the Serine-Carboxyl Peptidase Sedolisin through QM/MM Free Energy Simulations. 

The Journal of Physical Chemistry B 115(10):2470-2476.

Xu Z, Cai W & Cheng X (2011) Image Charge Method for Reaction Fields in a Hybrid Ion-Channel Model. 

Communication in Computational Physics 9(4):1056-1070.

Xu Z, Cheng X & Yang H (2011) Treecode-Based Generalized Born Method. Journal of Chemical Physics

134(6):064107.

Yao J, Nellas R, Glover MM & Shen T (2011) Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains. Biochemistry 50(19):4097-4104.

Yao J, Xu Q, Chen F & Guo H (2011) QM/MM Free Energy Simulations of Salicylic Acid Methyltransferase: 

Effects of Stabilization of TS-like Structures on Substrate Specificity. The Journal of Physical Chemistry B

115(2):389-396.

Zahran M, Berezniak T, Imhof P & Smith JC (2011) Role of Magnesium Ions in DNA Recognition by the EcoRV 

Restriction Endonuclease. FEBS Letters 585(17):2739-2743.

Miao Y & Baudry J (2011) Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process. Biophysical Journal 101(6):1493-1503

Ellingson SR & Baudry J (2011) High-Throughput Virtual Molecular Docking: Hadoop Implementation of 

AutoDock4 on a Private Cloud. ECMLS 2011 Proceedings of the second international workshop on Emerging 

computational methods for the life sciences.

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Cheng X & Ivanov I (in press) Molecular Dynamics (Springer).

Guo H-B, Parks J, Johs A & Smith JC (in press) Mercury Detoxification by Bacteria: Simulations of Transcription Activation and Mercury-Carbon Bond Cleavage in Modeling of Molecular Properties (Springer).

Mostofian B, Smith JC & Cheng X (in press) The Solvation Structures of Cellulose Microfibrils in Ionic Liquids. Interdisciplinary Sciences - Computational Life Sciences.

Noé F, Doose S, Daidone I, Lollmann M, Sauer M, Chodera JD & Smith JC (in press) Dynamical Fingerprints: 

Probing Individual Relaxation Processes in Biomolecular Dynamics with Simulations and Kinetic Experiments. Proceedings of the National Academy of Sciences.

Parks JM, Imhof P & Smith JC (in press) Understanding Enzyme Catalysis Using Computer Simulation. Encyclopedia of Catalysis, 2nd edition. (Wiley).

Prinz J-H, Held M, Smith JC & Noé F (in press) Efficient Computation, Sensitivity and Error Analysis of Committor Probabilities for Complex Dynamical Processes. Multiscale Modeling and Simulation.

Smith JC, Krishnan M, Petridis L & Smolin N (in press) Structure and Dynamics of Biological Systems: Integration of Neutron Scattering with Computer Simulation. Dynamics of Soft Matter.

Brothers MC , Nesbitt AE, Hallock MJ, Rupasinghe SG, Tang M, Harris J, Baudry J, Schuler MA & Rienstra CM 

(in press) VITAL NMR: Using Chemical Shift Derived Secondary Structure Information for a Limited Set of 

Amino Acids to Assess Homology Model Accuracy. J. Biomolecular NMR.

Hu X, Norris A, Baudry J, Serpersu E (in press) Coenzyme-A Binding to the Aminoglycoside Acetyltransferase (3)-IIIb Increases Conformational Sampling of Antibiotic Binding Site. Biochemistry.

Hu X, Elgobasho-Meinhardt N, Gembris D & Smith JC. (in press) Response of Water to Electric Fields at Temperatures below the Glass Transition: A Molecular Dynamics Analysis. Journal of Chemical Physics.

Bondar AN, Knapp-Mohammady M, Fische S & Smith JC (in press) Ground-state properties of the retinal 

molecule: from quantum mechanical to classical mechanical computations of retinal proteins. Theoretical 

Chemistry Accounts.

Sangha AK, Petridis L, Smith JC, Ziebell A & Parks JM (in press) Molecular simulation as a tool for studying 

lignin Environmental Progress and Sustainable Energy.

Pool R, Feenstra KA, Hoefling M, Schulz R, Smith JC & Heringa J (in press). Enabling grand-canonical Monte 

Carlo: extending the flexibioity of GROMACS through the GromPy Python Interface module to the GROMACS simulation C-library. Journal of Computational Chemistry.

Hong L, Lindner B, Smolin N, Sokolov A & Smith JC (in press) Three classes of motion in the dynamic 

neutron-scattering susceptibility of a globular protein. Physical Review Letters.

Ulmschneider J, Smith JC, White S & Ulmschneider M (in press) In Silico Partitioning and Transmembrane 

Insertion of Hydrophobic Peptides Under Equilibrium Conditions. Journal of the American Chemical Society.

Johs A, Harwood IM, Parks JM, Smith JC, Liang L & Miller SM. (in press) Structural characterization of intramolecular Hg2+ transfer between flexibly-linked domains of mercuric ion reductase. Journal of Molecular 

Biology.

Guo HB, Parks JM, Johs A & J.C. Smith JC (in press) Mercury Detoxification by Bacteria: Simulations of Transcription Activation and Mercury-Carbon Bond Cleavage in Modeling of Molecular Properties. Springer.

Thurkal L, Daidone I & Smith JC (in press) Structured pathway across the transition state for pep-tide folding 

revealed by molecular dynamics simulations. PLoS Computational Biology.

Srinivas G, Cheng X & Smith JC (in press) A solvent-free coarse-grain model for crystalline and amorphous 

cellulose fibrils. Journal of Computational Chemistry.

Smith JC, Krishnan M, Petridis L, Smolin N (2011) Integration of neutron scattering with computer simulation to study the structure and dynamics of biological systems. Dynamics of Biological Macromolecules by 

Neutron Scattering, ed. S. Magazu, Bentham Science Publishers, 95-104.

Klein H, Cheng X, Smith JC & Shen T (2011) Transfer matrix approach to the hydrogen-bonding in cellulose 

Iα fibrils describes the recalcitrance to thermal deconstruction. Journal of Chemical Physics. 135, 085106.

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Postdoctoral Fellows

Derek J. Cashman

Postdoctoral Fellow, since 1/2011

cashmandj@ornl.gov

John Eblen

Postdoctoral Fellow, since 1/2011

eblenjd@ornl.gov

Hao-Bo Guo

Postdoctoral Fellow, since 1/2008

guoh1@ornl.gov

Liang Hong

Postdoctoral Fellow, since 6/2010

hongl@ornl.gov

Yinglong Miao

Postdoctoral Fellow, since 9/2009

miaoy@ornl.gov

Ricky B. Nellas

Postdoctoral Fellow, since 1/2010

rbe@ornl.gov

Xianghong ‘Hanna’ Qi 

Research Associate, since 05/2011

qix1@ornl.gov

Demian Riccardi

Postdoctoral Fellow, since 1/2011

riccardidm@ornl.gov

Amandeep K. Sangha

Postdoctoral Fellow, since 6/2010

sanghaak@ornl.gov

Goundla Srinivas 

Postdoctoral Fellow, since 9/2011 

srinivasg@ornl.gov

Qin Xu

Postdoctoral Fellow, since 11/2010

xuq1@ornl.gov

Zheng Yi

Postdoctoral fellow, since 10/2009

yiz1@ornl.gov

Graduate Students

Dennis C. Glass 

Graduate Student, since 1/2009

glassdc@ornl.gov

Benjamin Lindner

Graduate Student, since 8/2007

lindnerb@ornl.gov

Barmak Mostofian

Graduate Student, since 1/2008

bmk@ornl.gov

Roland Schulz

Graduate Student, since 8/2007

roland@utk.edu

Xiaohu Hu

Graduate Student, since 8/2009

hux2@ornl.gov

Jason B. Harris

Graduate Student, since 8/2010

jharri43@utk.edu

Sally Ellingson

Graduate Student, since 8/2010

sellings@utk.edu

52
Administration

Julia B. Cooper

Administrative Assistant, 

since 8/2006

cooperjb@ornl.gov

System Administration

Michael D. Galloway

System Administrator, 

since 8/2006

gallowaymd@ornl.gov

Steve Moulton

System Administrator, 

since 1/2011

moultonsa@ornl.gov

Alumni

Barbara Collignon

Postdoctoral Fellow, 

10/2008 to 10/2011

Dan Mihailescu

Visiting Researcher, 

2006

Kei Moritsugu

Postdoctoral Fellow, 

4/2007 to 4/2008

Krishnan Marimuthu

Postdoctoral Fellow, 

4/2007 to 4/2010

Saharay Moumita

Postdoctoral Fellow, 

4/2007 to 4/2010

Nikolai Smolin

Postdoctoral Fellow, 

11/2008 to 9/2011

Christopher Topham

Visiting Researcher, 

2006

Jiancong Xu

Postdoctoral Fellow, 

9/2007 to 8/2009

53

Short-term Students and the China Connection:

A large number of graduate and undergraduates have passed through 

CMB over the last five years, doing rotations or more extended research. 

Jerome Baudry, in particular, has typically hosted five to seven rotation 

students each summer. Most of the students have come from UT, but 

we have also hosted students from Cambridge and Heidelberg Universities. Also, we have a developing relationship with Shanghai Jiao-Tong 

University, which Xiaolin Cheng, Hong Guo and Jeremy Smith visited in 

March 2011. Two Jiao-Tong graduate students are currently on extended 

research stays at CMB. 
CMB External Funding

DOE - Office of Biological and 

Environmental Science (OBER)

Title: ORNL Scientific Focus Area 

“Biofuels”

Funding period: 10/1/2010-10/1/2013

Jeremy C. Smith: Co-PI

DOE – OBER

Title: Bioenergy Science Center

Funding Period: 2007-2012

Jeremy C. Smith: Task Leader

NSF - IGERT

Title: SCALE-IT

(Scalable Computing and Leading Edge Innovative Technologies) for Biology

Funding Period: 10/2008-10/2013

Jeremy C. Smith: Co-PI

DOE – EpsCOR 

Implementation Award

Title: DE-FG02-08ER46528 Neutron Scattering Research Network for EPSCoR

States

Funding Period: 10/1/2008-10/1/2011

Jeremy C. Smith: Co-PI

NSF 07-597 EF - BIO CENTERS

Title: Nimbios – 

Center for Synthesis of 

Mathematics and Biology

Funding Period: 10/1/2008-10/1/2012

Jeremy C. Smith: Senior Personnel

DOE - OBER Science Focus Area

Title: Biogeochemical and Molecular Mechanisms Controlling 

Contaminant Transformation in the Environment

Funding Period: 10/2009-10/2014

Jeremy C. Smith: Co-PI and Task leader

NIH - PEER

Title: Program for Excellence and Equity in Research

Funding Period: 01/01/2009-01/01/2014

Jeremy C. Smith: Senior Personnel

DOE - Advanced Scientific Computing Research 

(ASCR)

Title: LAB 08-19 Software Development 

Tools for Improved Ease-of-Use of Petascale Systems ERKPE92 Scalable Development Environment for Petascale Computing

Funding Period: 09/2009-09/2012

Jeremy C. Smith: Co-PI

DOE – Laboratory 

Directed Research and 

Development Fund

Title: Neutron scattering methodologies 

for the study of protein dynamics 

Funding Period: 10/1/2009-10/1/2012

Jeremy C. Smith: PI
DOE – Laboratory Directed Research and 

Development Fund

Title: A Systems Biology Approach to 

Study Metabolic and Energetic Interdependencies in the Ignicoccus-Nanoarchaeum

System

Funding Period: 10/1/2009-10/01/2011

Jeremy C. Smith: Co-PI

Deutsche Forschungegemeinschaft: Excellence 

Initiative Dritte Säule: 

Internationale Zusammenarbeit

Title: International cooperation

Funding Period: 01/2009-01/2013

Jeremy C. Smith: PI

DOE- OBER/ASCR

Title: ERKJE84 and 

ERKPE84 Multiscale 

Mathematics for the Simulation of Complex Biological Systems

Funding Period: 09/2009-09/2012

Jeremy C. Smith: PI

NSF Award Biosystems Cluster 

No. MCB-0842871

Title: Integration of Computer 

Simulation and Neutron Scattering in the 

Characterization of Protein Dynamics

Funding Period: 8/1/2009-7/31/2012

Jeremy C. Smith: PI

Hong Guo: Co-PI

DOE Subsurface Biogeochemical 

Research

Title: Molecular Mechanisms of Bacterial 

Mercury Transformation

Funding Period: 08/2010-08/2013

Jeremy C. Smith: PI

DOE - OBER

Title: Program Announcement 

LAB 07-12 New Analytical and Imaging 

Technologies for Lignocellulosic Material Degradation, and for Multiplexed 

Screening for Plant Phenotypes ERKP704 

“Dynamic Visualization of Lignocellulose 

Degradation by Integration of Neutron 

Scattering Imaging and Computer Simulation”

Funding Period: 10/1/2007-10/1/2010

Jeremy C. Smith: Co-PI

DOE – Laboratory 

Directed Research 

and Development 

Fund: Systems Biology

Title: Computational Methods for Molecular Biophysics

Funding Period: 10/1/2006-10/1/2009

Jeremy C. Smith: PI

NIH – U54: No. UL1RR031975-01

Title: Novel Translational Methodologies (NTM) 

Funding Period: 07/01/2010-03/31/2012

Jerome Baudry & Jeremy C. Smith: Task 

Leader

NIH-R01 – GM072285-06 

Title: Computational Genomics of 

Signal Transduction

Funding Period: 04/01/2010 – 03/31/2014

Jerome Baudry: Co-PI

55
Supercomputer Allocations

Cellulosic Ethanol: Simulation of Multicomponent Biomass System

Organization: INCITE

Allocation: 30 million CPU hours

Platform: Jaguar, Lens (NCCS)

PI: Jeremy C. Smith

Molecular Dynamics Simulations of Protein Dynamics and Virtual 

High-Throughput Screening of Estrogenic Compounds

Organization: NERSC

Allocation: 5 million CPU hours

Platform: Hopper, Franklin, Carver (NERSC)

Co-PIs: Jeremy C. Smith, Jerome Baudry

Docking and Molecular Dynamics Simulation of Biomolecules

Organization: TeraGrid

Allocation: 4.7 million CPU hours

Platform: Kraken, Nautilus (NICS)

PI: Jerome Baudry

QM/MM Study of Sedolisins

Organization: TeraGrid

Allocation: 200 thousand CPU hours

Platform: Ranger (TACC)

PI: Hong Guo

56
Amazon Cloud Computing Award: 

Virtual High-Throughput Docking using Cloud Infrastructure

Organization: Amazon

Allocation: 7500 CPU hours

Platform: EC2

PI: Jerome Baudry

ANTON Computing Award: Investigation of Chemotaxis Initiation

Organization: DESRES

Allocation: 50 thousand CPU hours

Platform: ANTON

PI: Jerome Baudry

High Performance Computing for Rational Drug Discovery and Design

Supercomputing molecular discovery of prostate cancer molecular effectors

Organization: NCCS

Allocation: 5.8 million CPU hours

Platform: Jaguar

Task Leader: Jerome Baudry

57
58
Awards

Jerome Baudry

Outstanding Teaching Award for Junior Faculty 2011

Jerome Baudry received the Outstanding Teaching Award for Junior 

Faculty 2011 at the University of Tennessee Knoxville. Through this 

award, the BCMB faculty acknowledges faculty members who demonstrate a commitment and excellence in teaching at the undergraduate level.

Sally Ellingson

NSF funded Broader Engagement Grant 2011

NSF funded Scholarship / ACM student research 

competition GHC 2011

Sally Ellingson received an NSF funded Broader Engagement grant to 

attend Supercomputing 11 in Seattle, WA, and a NSF funded scholarship to attend the Grace Hopper Celebration 11 in Portland, OR to 

present her work in the Baudry lab on developing Cloud strategies for 

virtual docking.

Julia Cooper

ORNL divisional award

Julia Cooper received the ORNL Biosciences Divisional Administrative Award in 2009 for her role in the establishment and continued 

operation of CMB. 

59

Designed and edited by: 

Thomas Splettstößer

www.scistyle.com

Composed and edited by: 

Benjamin Lindner, Jeremy C. Smith

Contact

Center for Molecular Biophysics, 

Oak Ridge National Laboratory 

6011 Bethel Valley Road

Oak Ridge, Tennessee, 37830

Tel.: +1 865 574 6308

Fax: +1 865 576 7651

Email: cooperjb@ornl.gov (Julia Cooper)