NanoLSI Open Seminarrecommended by Prof. Alexander Mikhailov (PI of NanoLSI)

Program
TALK 1
2:00PM~ “Simulating life's key protein machines in metabolicand genetic control”

Dr. Jin Yu
Complex Systems Research Division,
Beijing Computational Science Research Center, Beijing

TALK 2“Using molecular simulation to understand theinterplay between molecular machine geometry and thekinetics of conformational changes”

3:10PM~

Dr. Jeffrey Noel
Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society,and Max Delbrück Center for Molecular Medicine, Berlin

Date and Time
2:00-4:10 PM, Tuesday, March 13, 2018
Venue
The 5th lecture room,
Natural Science and Technology Hall 5【Organizer】

Nano Life Science Institute (NanoLSI)【Contact】
Nano Life Science InstituteSeizo Morita smorita@staff.kanazawa-u.ac.jp

NanoLSI Open Seminarrecommended by Prof. Alexander Mikhailov (PI of NanoLSI)“Simulating Life’s Key Protein Machines in Metabolic and Genetic Control”
Jin YuBeijing Computational Science Research Center, Complex System Research
Division, Beijing 100193 China jinyu@csrc.ac.cn

Bio-molecular machines are made of nano- to micrometer scale protein complexes asmechano- chemical vehicles with energy self-sufficiency. My researches have been focusedon physical mechanisms of these naturally evolved machines, for example, on how they
maintain sufficiently high energy efficiency and accuracy despite of environmental noises
and fluctuations. Advancements in single molecule technologies and high-resolution
structural characterizations in recent years have made individual moleculeinterrogations possible [1]. On the other hand, physicists also started pondering about
the internal complexities and operations of these microscopic machines above the proof ofprinciples [2]. By utilizing a spectrum of molecular modeling and simulation techniques,
high-performance computing, along with statistical mechanics and stochastic methods,
we aim at providing physical insights of life’s fundamental machines as well as exploring
artificial design strategies for bio-medical advancements [3]. Here I will briefly introduce
two types of molecular machines we have recently studied: A highly efficient metabolic
machine that achieves sequential ATP hydrolyses around its protein ring to further
enable a rotor in the center [4], and a smallest transcription machine that moves along
DNA to synthesize RNA so that to transcribe the genetic information from DNA to RNA[5,6].
[1] C Bustamante, W Cheng and YX Mejia. Revisiting the Central Dogma One Molecule at a Time. Cell
2011 (144) 480[2] D Chowdhury. Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary
enterprise from a physicist's perspective. Physics Reports 2013 (529) 1[3] J Yu. Coordination and control inside simple biomolecular machines. In Protein Conformation
Dynamics, Advances in Experimental Medicine and Biology, by Springer 2014 (805) 353[4] L Dai, H Flechsig, and J Yu. Deciphering intrinsic inter-subunit couplings that lead to sequential
hydrolysis of F1-ATPase ring. Biophysical Journal 2017 (113) 1440
[5] J Yu. Computational investigations on polymerase actions in gene transcription and replication:
Combining physical modeling and atomistic simulations. Chinese Physics B 2016 (25) 018706[6] L-T Da, C E, Y Shuai, S Wu, X-D Su, and J Yu. T7 RNA polymerase translocation is facilitated byhelix opening on the fingers domain that may also prevent backtracking. Nucleic Acids Research 2017 (45)7909 equal contribution【Organizer】

Nano Life Science Institute (NanoLSI)【Contact】
Nano Life Science InstituteSeizo Morita smorita@staff.kanazawa-u.ac.jp

NanoLSI Open Seminarrecommended by Prof. Alexander Mikhailov (PI of NanoLSI)“Using molecular simulation to understand the interplay between molecularmachine geometry and the kinetics of conformational changes”
Jeffrey NoelFritz Haber Institute of the Max Planck Society and the Max Delbrück
Center for Molecular Medicine, Berlin

Conformational motions in molecular machines are often constrained by the shape ofthe molecule itself, which creates steric obstacles along transition paths betweenconformational states. Simplified molecular models with atomistic representation are
well suited to identifying the steric features important to conformational motions, which
can include regions of the molecular machine itself, or transiently-bound cofactors andsmall ligands. As a concrete example, I will describe how the shape of the ribosomal
accommodation tunnel, through which aa-tRNA makes a 12 nm motion during mRNAtranslation, includes steric features that lead to robust free energy barriers along thetRNA transition path. This effect is interpreted within an extended kinetic model ofaccommodation and it is shown how EF-Tu can contribute to efficient and accurate
kinetic proofreading, a process which has long eluded a molecular description. In a second
part, I will discuss current work in Berlin to understand dynamin, a polymeric molecularmachine able to form helical assemblies around membrane tubes and catalyze theirscission. I will discuss the results of our computational model of dynamin helices in thecontext of AFM (T. Ando et al.) and optical (A. Roux et al.) experiments on long helicalassemblies.

【Organizer】

Nano Life Science Institute (NanoLSI)【Contact】
Nano Life Science InstituteSeizo Morita smorita@staff.kanazawa-u.ac.jp