General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model.

ABSTRACT: Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. However, despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high specificity. Here, we present such a model that combines chemistry, mechanics, and genetics and explains how their interplay governs the evolution of specific protein-ligand interactions. The model shows that there are many routes to achieving molecular discrimination-by varying degrees of flexibility and shape/chemistry complementarity-but the key ingredient is precision. Harder discrimination tasks require more collective and precise coaction of structure, forces, and movements. Proteins can achieve this through correlated mutations extending far from a b

SUBMITTER: McBride JM 

PROVIDER: S-EPMC9641994 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature