TY - JOUR
T1 - Methodology for the Simulation of Molecular Motors at Different Scales
AU - Singharoy, Abhishek
AU - Chipot, Christophe
N1 - Funding Information:
The present contribution is dedicated to Klaus Schulten (1947-2016), whose visionary developments in parallel molecular dynamics allow biological motors to be simulated today over realistic time scales by means of petascale computing. The authors are indebted to Mahmoud Moradi, Wensheng Cai, and Peng Liu for stimulating discussions. The research reported here has been supported by the National Institute of Health through Grants 9P41GM104601 and R01- GM067887-11, and the National Science Foundation through Grants MCB1616590 and PHY1430124. The authors also acknowledge supercomputer time on Stampede provided by the Texas Advanced Computing Center (TACC) at the University of Texas at Austin through Extreme Science and Engineering Discovery Environment (XSEDE) Grants XSEDE MCA93S028. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05- 00OR22725. The authors are also thankful to the Centre Informatique National de l'Enseignement Supérieur (CINES) and the Grand Équipement National de Calcul Intensif (GENCI) for generous provision of computer time. C.C. acknowledges support from the Fonds Européen de Développement Régional (FEDER). A.S. is grateful for financial support from the Beckman Foundation, and the NSF through the Center for Physics of Living Cells.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2017/4/20
Y1 - 2017/4/20
N2 - Millisecond-scale conformational transitions represent a seminal challenge for traditional molecular dynamics simulations, even with the help of high-end supercomputer architectures. Such events are particularly relevant to the study of molecular motors - proteins or abiological constructs that convert chemical energy into mechanical work. Here, we present a hybrid-simulation scheme combining an array of methods including elastic network models, transition path sampling, and advanced free-energy methods, possibly in conjunction with generalized-ensemble schemes to deliver a viable option for capturing the millisecond-scale motor steps of biological motors. The methodology is already implemented in large measure in popular molecular dynamics programs, and it can leverage the massively parallel capabilities of petascale computers. The applicability of the hybrid method is demonstrated with two examples, namely cyclodextrin-based motors and V-type ATPases.
AB - Millisecond-scale conformational transitions represent a seminal challenge for traditional molecular dynamics simulations, even with the help of high-end supercomputer architectures. Such events are particularly relevant to the study of molecular motors - proteins or abiological constructs that convert chemical energy into mechanical work. Here, we present a hybrid-simulation scheme combining an array of methods including elastic network models, transition path sampling, and advanced free-energy methods, possibly in conjunction with generalized-ensemble schemes to deliver a viable option for capturing the millisecond-scale motor steps of biological motors. The methodology is already implemented in large measure in popular molecular dynamics programs, and it can leverage the massively parallel capabilities of petascale computers. The applicability of the hybrid method is demonstrated with two examples, namely cyclodextrin-based motors and V-type ATPases.
UR - http://www.scopus.com/inward/record.url?scp=85020195607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020195607&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.6b09350
DO - 10.1021/acs.jpcb.6b09350
M3 - Article
C2 - 28423900
AN - SCOPUS:85020195607
SN - 1520-6106
VL - 121
SP - 3502
EP - 3514
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 15
ER -