Delaware, February 1, 2009

ContentInformation

1. Welcome message from Michela Taufer
2. Our protein-ligand complexes
3. The new Docking@Home Webpage
4. The new Docking@Home screensaver
5. Events and publications

Project name:
Docking@Home(D@H)
Project Webpage:
docking.cis.udel.edu
Project location:
University ofDelaware
Number ofvolunteers: 6,000

6. D@H history in a nutshell
7. Our future goals

Number of active
computers: 9,170

8. Supporting D@H
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Welcome message fromMichela Taufer
Dear Friends,
The past year has been a very busy year for the D@H team. TheDocking@Home team moved to the University of Delaware in fall 2008 andwas challenged with the purchase of new servers for the project and theinstallation of the software parts. Fortunately new members have been joining
the original team composed by me, Trilce Estrada, and Abel Licon. Trilceʼseffort in the past year has been terrific and has made possible the upgrade ofD@H from alpha to beta in such a short time. She is the main coordinator ofthe job submissions as well as the collection and analysis of returned data.
We will share Trilceʼs results with you soon! Abel is still working in the groupbut his Masterʼs thesis targets a different application than docking. We would
have never been able to have CHARMM working so smoothly with BOINC
without Abelʼs help in compiling and debugging the code.
Kevin Kreiser, a graduate student, and Robert Keller, an undergraduate
student, joined the group in fall 2007 and worked on the D@H screensaver.
Robert graduated in May 2008 and now is working for a local company. Kevinis now working on his PhD thesis and developing more intuitive humancomputer interfaces for D@H so that our volunteers can better learn thescience in the project and more easily interact with the project interface. Jason
Parrot graduated at the beginning of 2008 and left Delaware. Before leaving,
Jason helped us to put together and install the servers for the D@H project.
Now Andy Roosen, the system administrator at our department, is helping uswith the servers. Of course the science has always been an importantcomponent of our project. Obaidur Rahaman (Ramie) joined our team fromthe Department of Chemistry in spring 2008 and is helping Trilce and me toget real science out of our simulations.
2“Since the project went public, on September
2008, 6,000 volunteers have joined D@H”
Brian Flad and the D@H webpage developer team supervised by Dr.
Dannagal Young (University of Delawareʼs Interactive Media) have impressed
everyone with their terrific job on the webpage that was recently released.
Brian is still working with us to make sure that our webpage is a valuable tool
to share the science and the computer science in D@H with you all. A new
member of the team has just joined the team, Philip Saponaro. Philip is ajunior undergraduate student and is working with Trilce and Kevin to monitorthe system and increase the graphical content of the webpage.
Of course, we are still collaborating with our partners Charlie Brooks andRoger Armen on the scientific part of the project. They moved to the Universityof Michigan last year. We have been having long conversations with Rogerabout the work done with D@H and slowly we are getting our results to a pointthat we can soon present them to you. David Anderson visited us in August
2008 and we are working with him on an emulator of volunteer computing
projects that can help administrators to tune volunteer projects and make surethat volunteers get computation and credits.
Since the project went public, on September 2008, 6,000 volunteers havejoined. We have sampled docking results for two of our three proteins with asimple docking algorithm. We are ready for the third protein and more accurate
docking algorithms, so a lot of computation is available for our volunteers in
the next 12 months. So far we have been collecting more than 10,000 jobs perday! This is terrific and only possible because of your valuable support,patience, and commitment. Many kudos to all our D@H volunteers.
Enjoy the rest of this newsletter!
Michela3

Our protein-ligand complexes
The design of new pharmaceutical drugs relies on finding small molecules,
called ligands, which dock into proteins and play an essential role in turning
protein functions on or off. Finding candidate ligand structures in a wet lab isvery expensive and time consuming. Computer simulations are used toaccelerate this process and to reduce costs. However, the computational
search for putative drugs (i.e., ligands that dock well in a protein) is a search ina large space of potential conformations and, therefore, is a very time- andcompute-intensive process.
Docking@Home computationally searches the large space of potential ligand
conformations, reducing the time and cost required to design new drugs byseveral orders of magnitude. In this search, the protein and ligand can havedifferent size and flexibility and their characteristics can have an important
impact on the computational cost. Docking@Home considered an initial poolof proteins representing three levels of flexibility. The proteins are: Trypsin (26complexes), HIV Protease (30 complexes), and p38 alpha (12 complexes).
Figure 1 graphically shows the three proteins and their relative flexibility withrespect to each other.

Figure 1: the D@H proteins4Trypsin
Trypsin is a protease that breaks down other proteins in the digestive system.
Recent studies suggest that inhibitors of trypsin can have potential applicationin breast cancer treatment. In this terrible disease, trypsin-like proteases
activate Protease-Activated Receptor-2 (PAR2), a protein in the tumor cell
membrane. While activated, PAR2 causes the degradation of extracellularmatrix (ECM) resulting in the spread of the tumor cell from one place toanother (metastasis). Drugs can act as inhibitors by de-activating the trypsinlike protease and are therefore potential agents capable of stopping thespread of breast cancer [1]. Figure 2 shows the Trypsin and a small set ofligands that D@H considers in the simulations[1] J. McIlroy, B. Cullen, G. Kay, J. Nelson, W. Odlings, R. Spence, and B Walker. A Novel
Trypsin-like Enzyme in Breast Cancer. Biochem. Soc. Trans., 22(1):19S, 1994.

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1c1rFigure 2: Three Trypsin complexes with their ligand docked in the protein
5HIV ProteaseHIV protease (HIV PR) is a protein in the HIV virus that is essential for its
replication in human cells. During the process of building a new HIV virus
inside the human cell, HIV PR cleaves some newly synthesized viral protein ina particular fashion. The cleaved pieces are required to build a mature HIVvirus. HIV PR has been considered as a therapeutic target to prevent HIVproliferation. A drug that can bind to the active site of HIV PR or deactivate it insome way will eventually stop the replication of HIV virus in human cells.
These drugs are called protease inhibitors. Several protease inhibitors likesaquinavir, ritonavir, indinavir, and nelfinavir are available for the treatment ofHIV infection [2]. Figure 3 shows the HIV protease and a small set of ligandsthat D@H considers in the simulations.
[2] L. Montagnier. Historical Essay: A History of HIV Discovery. Science, 298(5599): 1727 –1728, 29 November 2002.

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Figure 3: Three HIV protease complexes with their ligand docked in the protein

6P38 alphaP38alpha is also known as SAPK2a and MAPK14. It is involved in theregulation of cellular stress responses as well as the control of proliferationand survival of many cell types. Several promising compounds that inhibit p38
alpha are being investigated as potential therapies for arthritic andinflammatory diseases [3]. Figure 4 shows the p38alpha and a small set ofligands that D@H considers in the simulations.
[3] Lee, M. R.; Dominguez, C. MAP kinase p38 inhibitors: clinical results and an intimate lookat their interactions with p38alpha protein. Curr Med Chem 2005, 12, 2979- 94.

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Figure 4: Three p38 alpha complexes with their ligand docked in the protein
7The newDocking@Home Website
Students from the University of Delawareʼs Interactive Media minor (AllisonCasey, Brian Flad, Brianna Higgins, Lucas Newman, and Wybens Titus)
dedicated their fall semester to creating a new website structure and designfor the Docking@Home website. After analyzing the results from volunteers
and our team surveys, they set out to create a highly organized, simplified,and unified layout. By the end of the semester, a fully operable proof-ofconcept website was completed. Since then, Brian has been working toimplement the teamsʼ work into the original content and BOINC supplied codeusing PHP and MySQL. He is also working on rewriting some parts of thewebsite to be more user friendly. Many thanks to all of the volunteers who
have been providing feedback throughout the project.

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The newDocking@Home screensaver
The Docking@Home screensaver and graphical application serve as a visualconfirmation of the volunteerʼs contribution to the science behindDocking@Home. Volunteers can view and manipulate 3D representations of
the protein and ligand structures. These structures can be viewed separately
as well as in their current docking configuration with respect to thecomputation being performed. Several visualization styles are also provided toaid in visualizing the physical structure of the molecules. Several metrics
related to the computation are available to the volunteers so that they may
monitor the jobʼs progress.
The Docking@Home graphical application and screensaver was developed byRobert Keller and Kevin Kreiser at the University of Delaware. The application
is written in OpenGL and is compatible with both Windows and Linux operating
systems. Through careful planning and discussion, the development team at
Docking@Home decided that an informative interactive graphical application
would be well suited to achieving our goals of educating our volunteers about
the docking procedure. We hope that as a result our volunteers will feelengaged in the science they are helping to progress.

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Events and publications
Our eventsDavid P. Anderson at the 1st
East Coast BOINC meeting

Our team organized the first-ever East Coast
meeting of BOINC on Friday, Aug. 29, at theUniversity of Delaware. David P. Anderson, thepioneer of the volunteer computing paradigm andBerkeley Open Infrastructure for Network
Computing (BOINC) of the University of California
at Berkeley, spoke at the event. Trilce, MarkSomers (University of Leiden), Michael P.
Cummings (University of Maryland - College Park),
Jack Shultz (National Academies) and Andrew
Gillette (The Foundation for Computational
Learning & Science), and Eric Myers (LIGO
Hanford Observatory) were invited speakers. We
had 45 attendees; some of them from theUniversity of Delaware and some from otheruniversities and other states. You can find more
about the event at:
http://gcl.cis.udel.edu/EastCoast08/“Our team organized the first-ever East Coast BOINC
meeting on August 2008”
10Our recent publications
M. Taufer, R.S. Armen, J. Chen, P.J. Teller, and C.L. Brooks III:
Computational Multi-Scale Modeling in Protein-Ligand Docking. IEEE
Engineering in Medicine and Biology Magazine, 2008 (In Press).
More about this paper: This paper summarizes the main scientific ideas
beyond D@H.
T. Estrada, O. Fuentes, and M. Taufer: A Distributed Evolutionary Method to
Design Scheduling Policies for Volunteer Computing. ACM SIGMETRICS
Performance Evaluation Review Journal, Volume: 36, Issue: 3, Pages: 40 –49, December 2008.
More about this paper: Trilce is always looking for better ways to distribute thecomputation among the volunteers. She presented part of this paper in a
conference last May. This paper looks at scheduling policies for thedistribution of jobs supported by genetic algorithms.

Our recent posters
We presented D@H in posters at three important events last year. First in May
at the MASPLAS workshop in Princeton, then in November at the researchbooth of the University of Delaware at SCʼ08, and finally in December at theComputer Science Day at our department in which we celebrate thesuccesses of our students in research. Trilce and Kevin had a lot of questions
from very excited students discovering D@H.

11Docking@Home history in anutshell“The ideas behind D@H were born in 2004 at theScripps Research Institute. Since then, the project
has grown.
This is the story of D@H in a nutshell.“Spring 2003: Michela Taufer works on a docking algorithm using CHARMM with
Mike Crowley and Dan Price at the Scripps Research Institute under thesupervision of Charlie Brooks. The algorithm is finished in fall and the teampublish a paper titled: “Study of an Accurate and Fast Protein-Ligand Docking
Algorithm based on Molecular Dynamics”. The main idea was to use idle cycles
for protein-ligand docking.
2004: Michela put aside the docking idea to implement Predictor@Home (the firstBOINC project). With Chahm An and Charlie Brooks, she took part in CASP
2004. The team was invited to present the idea of using volunteerʼs computersat the CASP meeting in Gaeta, Italy in December 2004.

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Chronology of D@H
2005: Michela moves to the University of Texas at El Paso (UTEP) as an assistantprofessor and starts designing Docking@Home based on her initial idea in thepaper published in 2004.
September 2005: The National Science Foundation awards funding for developing
D@H to Michela and a team of other three investigators. With this valuable
financial support, the D@H adventure can finally start!
September 2006: D@H is in alpha phase. A lot of challenges for Andre, Richard,Trilce, Karina, and Michela, the D@H team at UTEP.
October 2006: Cori and Atomic Booty design the D@H logo for our old Website.
Great logo!
November 2006: D@H at the Supercomputing 2006 conference. Posters of theproject are presented at the UTEP booth. A lot of questions and interest!
June 2007: The D@H team moves to the University of Delaware. The project issuspended for relocation. The time goes by too slowly without D@H!
November 2007: D@H at the Supercomputing 2007 conference. The project issuspended but we still present our work at the booth of the University ofDelaware. A lot of people encourage us to get back on our legs!
December 2007: New servers and new start for D@H in alpha phase. Jason helps alot with the installation.
September 2008: Docking@Home opens the creation of new accounts to all andmoves to beta phase. Finally we are crunching science! Our first target is theHIV protease. Kudos to Trilce for her great effort during the summer!
November 2008: D@H starts the distribution of a new protein, the Trypsin. Roger ismonitoring our results from U. Michigan and, at UDel, Ramie joins us to review
the science.
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Chronology of D@H
November 2008: D@H finally has a screensaver. Look at our YouTube video:
http://www.youtube.com/watch?v=0bcgPAV0R7s.
Kudos to Kevin and Robert for the great screensaver and the professional
YouTube voice-over.
November 2008: D@H at the Supercomputing 2008 conference. Yes, we are still
crunching, and this time we crunch science!
January 2009: New Year and new Webpage. Many many kudos to Brian and his teamfor this excellent piece of art!
January 2009: A new protein is ready for D@H, the p38 alpha!!!

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Our future goals
Yes, a lot of things have happened in the past year and we still have a lot in
store for D@H and our volunteers. First of all, we have a new docking
algorithm with more accurate representation of the solvent in which the ligands
dock in the protein. We are testing the algorithm in standalone and we plan tohave it ready for our volunteersʼ machines in March.
We are also working on methods to cluster all the results we are getting fromyou and summarize the science embedded in hundreds of thousands of files
in an easy and clear way for Roger and Ramie (our scientists).
Our volunteers are always in our thoughts and we will give you some more funwith a new interactive screensaver. A first prototype will be available at theend of Spring 2009.
Stay tuned with D@H!

“D@H is looking forward to a brighter future withnew proteins, new docking algorithms, and newscientific contributions.
Our volunteers are our colonna portante (in Italian itmeans cornerstone)”15

Supporting Docking@Home
Some of you asked us how you can help D@H. The easier way is to crunch
our science. D@H has been growing so fast because of our committed (andsometimes patient) volunteers. At the same time, D@H owes a lot to talented
students at the University of Delaware who spend nights and weekends
monitoring the system and working on new features. So far we have beenvery lucky because the National Science Foundation (NSF) supported us. Our
NSF funding will end on August 31, 2009. Since we are a not for-profit
organization and no private companies provide us with funds to pay thestudents working on the project, we must continuously search for new funds.
The support for a graduate student is $25,000 per year for a stipend anduniversity benefits. We are currently applying for new funds from the National
Science Foundation and other national agencies: we hope we will be able toreceive something in this highly competitive environment. If you want to know
more how to support a student working on D@H financially, get in touch withMichela Taufer at taufer@udel.edu.

Our Sponsors

NSF OCI #0802650

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This Newsletter
was written by …
Michela Taufer
Trilce Estrada
Brian Flad
Kevin Kreiser
and with the feedback and suggestions of the other members of the Global
Computing Lab at the University of Delaware.

http://gcl.cis.udel.edu
For questions contact us at: dockingadmin@cis.udel.edu

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