Large-scale in silico mutagenesis experiments reveal optimization of genetic code and codon usage for protein mutational robustness.

ABSTRACT:

Background

How, and the extent to which, evolution acts on DNA and protein sequences to ensure mutational robustness and evolvability is a long-standing open question in the field of molecular evolution. We addressed this issue through the first structurome-scale computational investigation, in which we estimated the change in folding free energy upon all possible single-site mutations introduced in more than 20,000 protein structures, as well as through available experimental stability and fitness data.

Results

At the amino acid level, we found the protein surface to be more robust against random mutations than the core, this difference being stronger for small proteins. The destabilizing and neutral mutations are more numerous in the core and on the surface, respectively,

SUBMITTER: Schwersensky M 

PROVIDER: S-EPMC7576759 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature