Premium
Accelerated molecular dynamics simulations of protein folding
Author(s) -
Miao Yinglong,
Feixas Ferran,
Eun Changsun,
McCammon J. Andrew
Publication year - 2015
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23964
Subject(s) - molecular dynamics , protein folding , ww domain , folding (dsp implementation) , microsecond , downhill folding , chemistry , contact order , villin , force field (fiction) , crystallography , protein dynamics , phi value analysis , chemical physics , biophysics , computational chemistry , computer science , physics , biochemistry , biology , actin , astronomy , artificial intelligence , electrical engineering , gene , engineering
Folding of four fast‐folding proteins, including chignolin, Trp‐cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred‐of‐microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2–2.1 Å of the native NMR or X‐ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second‐order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein‐folding studies. © 2015 Wiley Periodicals, Inc.