Atomistic simulation of protein evolution reveals sequence covariation and time-dependent fluctuations of site-specific substitution rates.

ABSTRACT: Thermodynamic stability is a crucial fitness constraint in protein evolution and is a central factor in shaping the sequence landscapes of proteins. The correlation between stability and molecular fitness depends on the mechanism that relates the biophysical property with biological function. In the simplest case, stability and fitness are related by the amount of folded protein. However, when proteins are toxic in the unfolded state, the fitness function shifts, resulting in higher stability under mutation-selection balance. Likewise, a higher population size results in a similar change in protein stability, as it magnifies the effect of the selection pressure in evolutionary dynamics. This study investigates how such factors affect the evolution of protein stability, site-specific mutati

SUBMITTER: Norn C 

PROVIDER: S-EPMC10075473 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature