Biology subjects

Alpay, B. A.

Publications and source records attributed to Alpay, B. A..

2 recordsLinked to original sources

bioRxiv2025

Amino acid exchangeability and surface accessibility underpin the effects of single substitutions

Deep mutational scans have measured the effects of many mutations on many different proteins. Here we use a collection of such scans to perform a statistical meta-analysis of the effects of single amino acid substitutions. Specifically, we model the relative deleteriousness of each substitution in each deep mutational scan with respect to the identities of the wildtype and mutant residues, and the wildtype residues surface accessibility. This model explains much of the variance in mutational effects and quantifies physicochemical trends underlying them, including by yielding an empirical amino acid exchangeability matrix.

bioinformatics↗

bioRxiv2024

Effects of selection stringency on the outcomes of directed evolution

Directed evolution makes mutant lineages compete in climbing complicated sequence-function landscapes. Given this underlying complexity it is unclear how selection stringency, a ubiquitous parameter of directed evolution, impacts the outcome. Here we approach this question in terms of the fitnesses of the candidate variants at each round and the heterogeneity of their distributions of fitness effects. We show that even if the fittest mutant is most likely to yield the fittest mutants in the next round of selection, diversification can improve outcomes by sampling a larger variety of fitness effects. We find that heterogeneity in fitness effects between variants, larger population sizes, and evolution over a greater number of rounds all encourage diversification.

bioengineering↗