Automated selection of stabilizing mutations in designed and natural proteins.

ABSTRACT: The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We f

SUBMITTER: Borgo B 

PROVIDER: S-EPMC3277135 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature