Computational design of Candida boidinii xylose reductase for altered cofactor specificity.

ABSTRACT: In this study we introduce a computationally-driven enzyme redesign workflow for altering cofactor specificity from NADPH to NADH. By compiling and comparing data from previous studies involving cofactor switching mutations, we show that their effect cannot be explained as straightforward changes in volume, hydrophobicity, charge, or BLOSUM62 scores of the residues populating the cofactor binding site. Instead, we find that the use of a detailed cofactor binding energy approximation is needed to adequately capture the relative affinity towards different cofactors. The implicit solvation models Generalized Born with molecular volume integration and Generalized Born with simple switching were integrated in the iterative protein redesign and optimization (IPRO) framework to drive the redesign

SUBMITTER: Khoury GA 

PROVIDER: S-EPMC2786976 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature