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Temperature dependence of the free energy landscape of the src‐SH3 protein domain
Author(s) -
Guo Weihua,
Lampoudi Sotiria,
Shea JoanEmma
Publication year - 2004
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.20053
Subject(s) - energy landscape , lattice protein , folding (dsp implementation) , chemical physics , protein folding , downhill folding , sh3 domain , chemistry , hydrophobic effect , molecule , contact order , crystallography , molecular dynamics , phi value analysis , native state , computational chemistry , proto oncogene tyrosine protein kinase src , organic chemistry , biochemistry , kinase , electrical engineering , engineering
The temperature dependence of the free energy landscape of the src‐SH3 protein domain is investigated through fully atomic simulations in explicit solvent. Simulations are performed above and below the folding transition temperature, enabling an analysis of both protein folding and unfolding. The transition state for folding and unfolding, identified from the free energy surfaces, is found to be very similar, with structure in the central hydrophobic sheet and little structure throughout the rest of the protein. This is a result of a polarized folding (unfolding) mechanism involving early formation (late loss) of the central hydrophobic sheet at the transition state. Unfolding simulations map qualitatively well onto low‐temperature free energy surfaces but appear, however, to miss important features observed in folding simulations. In particular, details of the folding mechanism involving the opening and closing of the hydrophobic core are not captured by unfolding simulations performed under strongly denaturing conditions. In addition, free energy surfaces at high temperatures do not display a desolvation barrier found at lower temperatures, involving the expulsion of water molecules from the hydrophobic core. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.