Proteins’ Evolution upon Point Mutations

VILA, JORGE A.

ACS Omega

ACS

Año: 2022 vol. 7 p. 14371 - 14376

2470-1343

As the reader must be already aware state-of-the-art protein foldingprediction methods have reached a smashing success in their goal of accuratelydetermining the three-dimensional structures of proteins. Yet, a solution tosimple problems such as the effects of protein point mutations on their (i)native conformation; (ii) marginal stability; (iii) ensembleof high-energy native-like conformations, (iv) metamorphism propensity, and,hence, their evolvability, remain as an unsolved problem. As a plausiblesolution to the latter, some properties of the amide hydrogen-deuteriumexchange, a highly sensitive probe of the structure, stability, and folding ofproteins are assessed from a new perspective. The preliminary results indicatethat the protein marginal-stability change upon point mutations provides thenecessary and sufficient information to estimate, through a Boltzmann factor,the evolution of the amide hydrogen-exchange protection factors and,consequently, that of the ensemble of folded conformations coexisting with thenative state. This work contributes to our general understanding of the pointmutations´ effects on proteins and may spur significant progress in our effortsto develop methods to determine the appearance of new folds and functionsaccurately