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Updated: Apr 23, 2026

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Amino acid exchangeability and surface accessibility underpin the effects of single substitutions
Berk A Alpay1, Piyush Nanda2,3, Emma Nagy3
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, United States.
Abstract:
Deep mutational scans have measured the effects of many mutations on a large variety of proteins. We use a collection of these scans to perform a meta-analysis of the effects of single amino acid substitutions, modeling the relative deleteriousness of each substitution with respect to the surface accessibility of the wildtype residue and the identities of the amino acids being exchanged. This simple model quantifies physicochemical trends underlying mutational effects across proteins and phenotypes, and manages to explain much of the observed variance.
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