Kinetic definition of protein folding transition state ensembles and reaction coordinates.

Biophysical Journal
Christopher D SnowV S Pande

Abstract

Using distributed molecular dynamics simulations we located four distinct folding transitions for a 39-residue betabetaalphabeta protein fold. To characterize the nature of each room temperature transition, we calculated the probability of transmission for 500 points along each free energy barrier. We introduced a method for determining transition states by employing the transmission probability, Ptrans, and determined which conformations were transition state ensemble members (Ptrans approximately 0.5). The transmission probability may be used to characterize the barrier in several ways. For example, we ran simulations at 82 degrees C, determined the change in Ptrans with temperature for all 2,000 conformations, and quantified Hammond behavior directly using Ptrans correlation. Additionally, we propose that diffusion along Ptrans may provide the configurational diffusion rate at the top of the barrier. Specifically, given a transition state conformation x0 with estimated Ptrans=0.5, we selected a large set of subsequent conformations from independent trajectories, each exactly a small time deltat after x0 (250 ps). Calculating Ptrans for the new trial conformations, we generated the P(Ptrans|deltat=250 ps) distribution that re...Continue Reading

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Citations

Jan 15, 2010·Journal of the American Chemical Society·Vincent A VoelzVijay S Pande
Jul 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sara L Quaytman, Steven D Schwartz
Jan 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jae Shick YangEugene I Shakhnovich
Jun 25, 2008·Annual Review of Biophysics·Ken A DillThomas R Weikl
Apr 29, 2009·International Journal of Molecular Sciences·Ronald D Hills, Charles L Brooks
Jan 4, 2007·The Journal of Chemical Physics·Baron Peters
Oct 5, 2010·The Journal of Chemical Physics·Rui D M TravassoAntonio Rey
Feb 19, 2008·Biophysical Journal·Giovanni Settanni, Alan R Fersht
Sep 10, 2014·Molecular Simulation·Wenjin Li, Ao Ma
Nov 17, 2015·The Journal of Chemical Physics·Polina V Banushkina, Sergei V Krivov
Sep 16, 2009·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Patrícia F N Faísca
Dec 12, 2012·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Xuewei JiangYi Xiao
Dec 31, 2008·The Journal of Physical Chemistry. B·Lijiang YangYi Qin Gao
Jan 28, 2015·Accounts of Chemical Research·Diwakar ShuklaVijay S Pande
May 20, 2011·Journal of the American Chemical Society·Elias Ahadi, Lars Konermann

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