Long-timescale molecular dynamics simulations of protein structure and function

被引:596
作者
Klepeis, John L. [1 ]
Lindorff-Larsen, Kresten [1 ]
Dror, Ron O. [1 ]
Shaw, David E. [1 ,2 ]
机构
[1] DE Shaw Res, New York, NY 10036 USA
[2] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA
关键词
FORCE-FIELD; MECHANISM; HYDRATION; ENSEMBLE; MOTIONS; MODEL;
D O I
10.1016/j.sbi.2009.03.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular dynamics simulations allow for atomic-level characterization of biomolecular processes such as the conformational transitions associated with protein function. The computational demands of such simulations, however, have historically prevented them from reaching the microsecond and greater timescales on which these events often occur. Recent advances in algorithms, software, and computer hardware have made microsecond-timescale simulations with tens of thousands of atoms practical, with millisecond-timescale simulations on the horizon. This review outlines these advances in high-performance molecular dynamics simulation and discusses recent applications to studies of protein dynamics and function as well as experimental validation of the underlying computational models.
引用
收藏
页码:120 / 127
页数:8
相关论文
共 61 条
[1]   Polarizable empirical force field for the primary and secondary alcohol series based on the classical drude model [J].
Anisimov, Victor M. ;
Vorobyov, Igor V. ;
Roux, Benoit ;
MacKerell, Alexander D., Jr. .
JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2007, 3 (06) :1927-1946
[2]   Mechanism of Na+/H+ antiporting [J].
Arkin, Isaiah T. ;
Xu, Huafeng ;
Jensen, Morten O. ;
Arbely, Eyal ;
Bennett, Estelle R. ;
Bowers, Kevin J. ;
Chow, Edmond ;
Dror, Ron O. ;
Eastwood, Michael P. ;
Flitman-Tene, Ravenna ;
Gregersen, Brent A. ;
Klepeis, John L. ;
Kolossvary, Istvan ;
Shan, Yibing ;
Shaw, David E. .
SCIENCE, 2007, 317 (5839) :799-803
[3]   Are current molecular dynamics force fields too helical? [J].
Best, Robert B. ;
Buchete, Nicolae-Viorel ;
Hummer, Gerhard .
BIOPHYSICAL JOURNAL, 2008, 95 (01) :L7-L9
[4]   Relation between native ensembles and experimental structures of proteins [J].
Best, Robert B. ;
Lindorff-Larsen, Kresten ;
DePristo, Mark A. ;
Vendruscolo, Michele .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (29) :10901-10906
[5]  
Bhatia A., 2008, Proc. IEEE Int'l Conf. Network (ICON), P1, DOI [10.1002/9780470414811, DOI 10.1002/9780470414811]
[6]  
Bowers K. J., 2006, SC06 P 2006 ACM IEEE, P43, DOI DOI 10.1109/SC.2006.54
[7]   Zonal methods for the parallel execution of range-limited N-body simulations [J].
Bowers, Kevin J. ;
Dror, Ron O. ;
Shaw, David E. .
JOURNAL OF COMPUTATIONAL PHYSICS, 2007, 221 (01) :303-329
[8]   Peptide folding kinetics from replica exchange molecular dynamics [J].
Buchete, Nicolae-Viorel ;
Hummer, Gerhard .
PHYSICAL REVIEW E, 2008, 77 (03)
[9]   Importance of the CMAP correction to the CHARMM22 protein force field: Dynamics of hen lysozyme [J].
Buck, M ;
Bouguet-Bonnet, S ;
Pastor, RW ;
MacKerell, AD .
BIOPHYSICAL JOURNAL, 2006, 90 (04) :L36-L38
[10]   Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics [J].
Chodera, John D. ;
Singhal, Nina ;
Pande, Vijay S. ;
Dill, Ken A. ;
Swope, William C. .
JOURNAL OF CHEMICAL PHYSICS, 2007, 126 (15)