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Free energy surfaces of miniproteins with a ββα motif: Replica exchange molecular dynamics simulation with an implicit solvation model
Author(s) -
Jang Soonmin,
Kim Eunae,
Pak Youngshang
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20771
Subject(s) - molecular dynamics , solvation , replica , implicit solvation , maxima and minima , force field (fiction) , atom (system on chip) , protein folding , native state , statistical physics , chemistry , computational chemistry , topology (electrical circuits) , physics , computer science , crystallography , molecule , mathematics , quantum mechanics , art , mathematical analysis , biochemistry , visual arts , embedded system , combinatorics
Designed miniproteins with a ββα motif, such as BBA5, 1FSD, and 1PSV can serve as a benchmark set to test the validity of all‐atom force fields with computer simulation, because they contain all the basic structural elements in protein folding. Unfortunately, it was found that the standard all‐atom force fields with the generalized Born (GB) implicit solvation model tend to produce distorted free energy surfaces for the ββα proteins, not only because energetically those proteins need to be described by more balanced weights of the α‐ and β‐strands, but also because the GB implicit solvation model suffers from overestimated salt bridge effects. In an attempt to resolve these problems, we have modified one of the standard all‐atom force fields in conjunction with the GB model, such that each native state of the ββα proteins is in its free energy minimum state with reasonable energy barriers separating local minima. With this modified energy model, the free energy contour map in each protein was constructed from the replica exchange molecular dynamics REMD simulation. The resulting free energy surfaces are significantly improved in comparison with previous simulation results and consistent with general views on small protein folding behaviors with realistic topology and energetics of all three proteins. Proteins 2006. © 2005 Wiley‐Liss, Inc.