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Hydrogen‐bonding classes in proteins and their contribution to the unfolding reaction
Author(s) -
Ragone Raffaele
Publication year - 2001
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 - 10.1110/ps.09201
Subject(s) - side chain , hydrogen bond , chemistry , crystallography , protein folding , alkyl , protein structure , thermodynamics , computational chemistry , molecule , organic chemistry , polymer , biochemistry , physics
This paper proposes to assess hydrogen‐bonding contributions to the protein stability, using a set of model proteins for which both X‐ray structures and calorimetric unfolding data are known. Pertinent thermodynamic quantities are first estimated according to a recent model of protein energetics based on the dissolution of alkyl amides. Then it is shown that the overall free energy of hydrogen‐bond formation accounts for a hydrogen‐bonding propensity close to helix‐forming tendencies previously found for individual amino acids. This allows us to simulate the melting curve of an alanine‐rich helical 50‐mer with good precision. Thereafter, hydrogen‐bonding enthalpies and entropies are expressed as linear combinations of backbone‐backbone, backbone–side‐chain, side‐chain–backbone, and side‐chain–side‐chain donor‐acceptor contributions. On this basis, each of the four components shows a different free energy versus temperature trend. It appears that structural preference for side‐chain–side‐chain hydrogen bonding plays a major role in stabilizing proteins at elevated temperatures.