A computational method for design of connected catalytic networks in proteins.

ABSTRACT: Computational design of new active sites has generally proceeded by geometrically defining interactions between the reaction transition state(s) and surrounding side-chain functional groups which maximize transition-state stabilization, and then searching for sites in protein scaffolds where the specified side-chain-transition-state interactions can be realized. A limitation of this approach is that the interactions between the side chains themselves are not constrained. An extensive connected hydrogen bond network involving the catalytic residues was observed in a designed retroaldolase following directed evolution. Such connected networks could increase catalytic activity by preorganizing active site residues in catalytically competent orientations, and enabling concerted interactions be

SUBMITTER: Weitzner BD 

PROVIDER: S-EPMC6863703 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature