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Role of hydrophilic and hydrophobic contacts in folding of the second β‐hairpin fragment of protein G: Molecular dynamics simulation studies of an all‐atom model
Author(s) -
Zhou Yaoqi,
Linhananta Apichart
Publication year - 2002
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.10065
Subject(s) - molecular dynamics , chemistry , hydrogen bond , hydrophobic effect , protein folding , folding (dsp implementation) , chemical physics , crystallography , contact order , solvent models , atom (system on chip) , nucleation , downhill folding , computational chemistry , molecule , phi value analysis , native state , biochemistry , organic chemistry , computer science , embedded system , electrical engineering , engineering , solvation
Predicting the folding mechanism of the second β‐hairpin fragment of the Ig‐binding domain B of streptococcal protein G is unexpectedly challenging for simplified reduced models because the models developed so far indicated a different folding mechanism from what was suggested from high‐temperature unfolding and equilibrium free‐energy surface analysis based on established all‐atom empirical force fields in explicit or implicit solvent. This happened despite the use of empirical residue‐based interactions, multibody hydrophobic interactions, and inclusions of hydrogen bonding effects in the simplified models. This article employs a recently developed all‐atom (except nonpolar hydrogens) model interacting with simple square‐well potentials to fold the peptide fragment by molecular dynamics simulation methods. In this study, 193 out of 200 trajectories are folded at two reduced temperatures (3.5 and 3.7) close to the transition temperature T * ∼ 4.0. Each simulation takes <7 h of CPU time on a Pentium 800‐MHz PC. Folding of the new all‐atom model is found to be initiated by collapse before the formation of main‐chain hydrogen bonds. This verifies the mechanism proposed from previous all‐atom unfolding and equilibrium simulations. The new model further predicts that the collapse is initiated by two nucleation contacts (a hydrophilic contact between D46 and T49 and a hydrophobic contact between Y45 and F52), in agreement with recent NMR measurements. The results suggest that atomic packing and native contact interactions play a dominant role in folding mechanism. Proteins 2002;47:154–162. © 2002 Wiley‐Liss, Inc.