Hydrogen-bonding classes in proteins and their contribution to the unfolding reaction

This paper proposes to assess hydrogen-bonding contributions to the protein stability, using a set of model proteins for which both X-ray structures a nd calorimetric unfolding data are known. Pertinent thermodynamic quantitie s are first estimated according to a recent model of protein energetics bas ed on the dissolution of alkyl amides. Then it is shown that the overall fr ee energy of hydrogen-bond formation accounts for a hydrogen-bonding propen sity close to helix-forming tendencies previously found for individual amin o acids. This allows us to simulate the melting curve of an alanine-rich he lical 50-mer with good precision. Thereafter, hydrogen-bonding enthalpies a nd entropies are expressed as linear combinations of backbone-backbone, bac kbone-side-chain, side-chain-backbone, and side-chain-side-chain donor-acce ptor contributions. On this basis, each of the four components shows a diff erent free energy versus temperature trend. It appears that structural pref erence for side-chain-side-chain hydrogen bonding plays a major role in sta bilizing proteins at elevated temperatures.