Ten-microsecond MD simulation of a fast-folding WW domain

@article{citeulike:2553148, abstract = {All-atom molecular dynamics (MD) simulations of protein folding allow analysis of the folding process at an unprecedented level of detail. Unfortunately, such simulations have not yet reached their full potential both due to difficulties in sufficiently sampling the microsecond timescales needed for folding, and because the force field used may yield neither the correct dynamical sequence of events nor the folded structure. The ongoing study of protein folding through computational methods thus requires both improvements in the performance of molecular dynamics programs to make longer timescales accessible, and testing of force fields in the context of folding simulations. We report a ten-microsecond simulation of an incipient downhill-folding WW domain mutant along with measurement of a molecular time and activated folding time of 1.5 microseconds and 13.3 microseconds, respectively. The protein simulated in explicit solvent exhibits several metastable states with incorrect topology and does not assume the native state during the present simulations. 10.1529/biophysj.108.131565}, author = {Freddolino, Peter L. and Liu, Feng and Gruebele, Martin H. and Schulten, Klaus }, citeulike-article-id = {2553148}, comment = {Dan E. 5/14/08}, doi = {10.1529/biophysj.108.131565}, journal = {Biophys. J.}, keywords = {cpjc}, month = {March}, pages = {biophysj.108.131565+}, posted-at = {2008-05-13 18:47:51}, priority = {0}, title = {Ten-microsecond MD simulation of a fast-folding WW domain}, url = {http://dx.doi.org/10.1529/biophysj.108.131565}, year = {2008} }

TY - JOUR ID - citeulike:2553148 L3 - citeulike-article-id:2553148 TI - Ten-microsecond MD simulation of a fast-folding WW domain JF - Biophys. J. SP - biophysj.108.131565 N2 - All-atom molecular dynamics (MD) simulations of protein folding allow analysis of the folding process at an unprecedented level of detail. Unfortunately, such simulations have not yet reached their full potential both due to difficulties in sufficiently sampling the microsecond timescales needed for folding, and because the force field used may yield neither the correct dynamical sequence of events nor the folded structure. The ongoing study of protein folding through computational methods thus requires both improvements in the performance of molecular dynamics programs to make longer timescales accessible, and testing of force fields in the context of folding simulations. We report a ten-microsecond simulation of an incipient downhill-folding WW domain mutant along with measurement of a molecular time and activated folding time of 1.5 microseconds and 13.3 microseconds, respectively. The protein simulated in explicit solvent exhibits several metastable states with incorrect topology and does not assume the native state during the present simulations. 10.1529/biophysj.108.131565 KW - cpjc N1 - Dan E. 5/14/08 AU - Freddolino, Peter AU - Liu, Feng AU - Gruebele, Martin AU - Schulten, Klaus PY - 2008/03/13/ UR - http://dx.doi.org/10.1529/biophysj.108.131565 ER -