Fast, cheap and out of control--Insights into thermodynamic and informatic constraints on natural protein sequences from de novo protein design.

ABSTRACT: The accumulated results of thirty years of rational and computational de novo protein design have taught us important lessons about the stability, information content, and evolution of natural proteins. First, de novo protein design has complicated the assertion that biological function is equivalent to biological structure - demonstrating the capacity to abstract active sites from natural contexts and paste them into non-native topologies without loss of function. The structure-function relationship has thus been revealed to be either a generality or strictly true only in a local sense. Second, the simplification to "maquette" topologies carried out by rational protein design also has demonstrated that even sophisticated functions such as conformational switching, cooperative ligand bindi

SUBMITTER: Brisendine JM 

PROVIDER: S-EPMC4856154 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature