The simplicity of protein sequence-function relationships.

ABSTRACT: How complicated is the genetic architecture of proteins - the set of causal effects by which sequence determines function? High-order epistatic interactions among residues are thought to be pervasive, making a protein's function difficult to predict or understand from its sequence. Most studies, however, used methods that overestimate epistasis, because they analyze genetic architecture relative to a designated reference sequence - causing measurement noise and small local idiosyncrasies to propagate into pervasive high-order interactions - or have not effectively accounted for global nonlinearity in the sequence-function relationship. Here we present a new reference-free method that jointly estimates global nonlinearity and specific epistatic interactions across a protein's entire genotyp

SUBMITTER: Park Y 

PROVIDER: S-EPMC10508729 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature