Computational design of second-site suppressor mutations at protein-protein interfaces.

ABSTRACT: The importance of a protein-protein interaction to a signaling pathway can be established by showing that amino acid mutations that weaken the interaction disrupt signaling, and that additional mutations that rescue the interaction recover signaling. Identifying rescue mutations, often referred to as second-site suppressor mutations, controls against scenarios in which the initial deleterious mutation inactivates the protein or disrupts alternative protein-protein interactions. Here, we test a structure-based protocol for identifying second-site suppressor mutations that is based on a strategy previously described by Kortemme and Baker. The molecular modeling software Rosetta is used to scan an interface for point mutations that are predicted to weaken binding but can be rescued by mutatio

SUBMITTER: Sammond DW 

PROVIDER: S-EPMC2903445 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature