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Consistency in structural energetics of protein folding and peptide recognition
Author(s) -
Zhang Chao,
Cornette James L.,
Delisi Charles
Publication year - 1997
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560060512
Subject(s) - contact order , conformational entropy , entropy (arrow of time) , chemistry , protein folding , crystallography , thermodynamics , folding (dsp implementation) , molecule , chemical physics , physics , native state , biochemistry , organic chemistry , electrical engineering , engineering
We report a new free energy decomposition that includes structure‐derived atomic contact energies for the desolvation component, and show that it applies equally well to the analysis of single‐domain protein folding and to the binding of flexible peptides to proteins. Specifically, we selected the 17 single‐domain proteins for which the three‐dimensional structures and thermodynamic unfolding free energies are available. By calculating all terms except the backbone conformational entropy change and comparing the result to the experimentally measured free energy, we estimated that the mean entropy gain by the backbone chain upon unfolding (Δ S bb ) is 5.3 cal/K per mole of residue, and that the average backbone entropy for glycine is 6.7 cal/K. Both numbers are in close agreement with recent estimates made by entirely different methods, suggesting a promising degree of consistency between data obtained from disparate sources. In addition, a quantitative analysis of the folding free energy indicates that the unfavorable backbone entropy for each of the proteins is balanced predominantly by favorable backbone interactions. Finally, because the binding of flexible peptides to receptors is physically similar to folding, the free energy function should, in principle, be equally applicable to flexible docking. By combining atomic contact energies, electrostatics, and sequence‐dependent backbone entropy, we calculated a priori the free energy changes associated with the binding of four different peptides to HLA‐A2.1 MHC molecule and found agreement with experiment to within 10% without parameter adjustment.