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The role of protein “Stability patches” in molecular recognition: A case study of the human growth hormone‐receptor complex
Author(s) -
Osman Roman,
Mezei Mihaly,
Engel Stanislav
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.24276
Subject(s) - molecular recognition , entropy (arrow of time) , chemistry , intermolecular force , molecular dynamics , conformational entropy , surface protein , enthalpy , receptor , protein stability , biophysics , thermodynamics , molecule , biology , biochemistry , computational chemistry , physics , organic chemistry , virology
Dynamic characteristics of protein surfaces are among the factors determining their functional properties, including their potential participation in protein‐protein interactions. The presence of clusters of static residues—“stability patches” (SPs)—is a characteristic of protein surfaces involved in intermolecular recognition. The mechanism, by with SPs facilitate molecular recognition, however, remains unclear. Analyzing the surface dynamic properties of the growth hormone and of its high‐affinity variant we demonstrated that reshaping of the SPs landscape may be among the factors accountable for the improved affinity of this variant to the receptor. We hypothesized that SPs facilitate molecular recognition by moderating the conformational entropy of the unbound state, diminishing enthalpy–entropy compensation upon binding, and by augmenting the favorable entropy of desolvation. SPs mapping emerges as a valuable tool for investigating the structural basis of the stability of protein complexes and for rationalizing experimental approaches, such as affinity maturation, aimed at improving it. © 2015 Wiley Periodicals, Inc.