Amino acid exchangeability and surface accessibility underpin the effects of single substitutions
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.
Fields of Study & Subjects
RNA and protein synthesis mechanisms
DNA and Nucleic Acid Chemistry
Chemical Synthesis and Analysis
Publication details
- Journal / source
- Genetics
- Volume
- 233
- Issue
- 2
- Publication date
- 21 April 2026
- Language
- EN