Conformational Ensembles from Experimental Data and Computer Simulations

106 / 161

Conformational Ensembles from Experimental Data
and Computer Simulations Poster Abstracts
102
67-POS Board 27
Efficient Parallel Computation for Flexible Fitting of Cryo-EM Density Map
Takaharu Mori1,2, Osamu Miyashita3, Yuji Sugita1,2,3 .
1RIKEN Theor. Mol. Sci. Lab., Wako-shi, Japan, 3RIKEN AICS, Kobe-shi, Japan.2RIKEN
iTHES, Wako-shi, Japan,
Single-particle cryo-electron microscopy (cryo-EM) is one of the powerful experimental
techniques to determine structures of biomolecules at near atomic resolutions. The method does
not require crystallization of the sample, and the 3D structure of the target biomolecule is
reconstructed from a large number of 2D images. Molecular dynamics (MD) simulations have
been often used to construct 3D structures by fitting the all-atom model to low-resolution cryo-
EM density map. One of the major problems in such a flexible fitting simulation is that we need
large computational costs if we tackle big molecules like ribosome and protein complexes.
Recently, we have developed our in-house MD program package (GENESIS), which supports
various types of replica exchange molecular dynamics methods (REMD) as well as conventional
MD methods for large systems including hundreds million atoms [1]. In this study, we
introduced a new REMD algorithm for cryo-EM fitting, where the force constants of the biasing
potential are exchanged between a pair of replicas. The method can automatically adjust the
strength of the biasing force in each replica to avoid overfitting issues [2]. We also proposed a
new parallel computing algorithm for cryo-EM fitting with hybrid MPI/OpenMP schemes, where
the simulation system is decomposed into several domains according to the number of atoms in
the local spaces. We show performance of GENESIS in cryo-EM fitting simulations for large
systems such as membrane proteins and ribosomes.
[1] J. Jung*, T. Mori*, C. Kobayashi, Y. Matsunaga, T. Yoda, M. Feig, and Y. Sugita, WIREs
Comput. Mol. Sci., 5, 310-323 (2015).
[2] O. Miyashita, C. Kobayashi, T. Mori, Y. Sugita and F. Tama, J. Comput. Chem. DOI:
10.1002/jcc.24785