Beyond Thermodynamic Constraints: Evolutionary Sampling Generates Realistic Protein Sequence Variation.

ABSTRACT: Biological evolution generates a surprising amount of site-specific variability in protein sequences. Yet, attempts at modeling this process have been only moderately successful, and current models based on protein structural metrics explain, at best, 60% of the observed variation. Surprisingly, simple measures of protein structure, such as solvent accessibility, are often better predictors of site-specific variability than more complex models employing all-atom energy functions and detailed structural modeling. We suggest here that these more complex models perform poorly because they lack consideration of the evolutionary process, which is, in part, captured by the simpler metrics. We compare protein sequences that are computationally designed to sequences that are computationally evolve

SUBMITTER: Jiang Q 

PROVIDER: S-EPMC5887137 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature