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Folding mechanism of β‐hairpins studied by replica exchange molecular simulations
Author(s) -
Zhang Jian,
Qin Meng,
Wang Wei
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.20813
Subject(s) - replica , mechanism (biology) , folding (dsp implementation) , molecular dynamics , protein folding , biophysics , chemistry , chemical physics , physics , computational chemistry , biology , biochemistry , engineering , geography , electrical engineering , archaeology , quantum mechanics
The folding process of trpzip2 β‐hairpin is studied by the replica exchange molecular dynamics (REMD) and normal MD simulations, aiming to understand the folding mechanism of this unique small, stable, and fast folder, as well as to reveal the general principles in the folding of β‐hairpins. According to our simulations, the TS ensemble is mainly characterized by a largely formed turn and the interaction between the inner pair of hydrophobic core residues. The folding is a zipping up of hydrogen bonds. However, the nascent turn has to be stabilized by the partially formed hydrophobic core to cross the TS. Thus our folding picture is in essence a blend of hydrogen bond‐centric and hydrophobic core‐centric mechanism. Our simulations provide a direct evidence for a very recent experiment (Du et al., Proc Natl Acad Sci USA 2004;101:15915–15920), which suggests that the turn formation is the rate‐limiting step for β‐hairpin folding and the unfolding is mainly determined by the hydrophobic interactions. Besides, the relationship between hydrogen bond stabilities and their relative importance in folding are investigated. It is found that the hydrogen bonds with higher stabilities need not play more important roles in the folding process, and vice versa. Proteins 2006. © 2005 Wiley‐Liss, Inc.