High-resolution structural and thermodynamic analysis of extreme stabilization of human procarboxypeptidase by computational protein design.

ABSTRACT: Recent efforts to design de novo or redesign the sequence and structure of proteins using computational techniques have met with significant success. Most, if not all, of these computational methodologies attempt to model atomic-level interactions, and hence high-resolution structural characterization of the designed proteins is critical for evaluating the atomic-level accuracy of the underlying design force-fields. We previously used our computational protein design protocol RosettaDesign to completely redesign the sequence of the activation domain of human procarboxypeptidase A2. With 68% of the wild-type sequence changed, the designed protein, AYEdesign, is over 10 kcal/mol more stable than the wild-type protein. Here, we describe the high-resolution crystal structure and solution NMR s

SUBMITTER: Dantas G 

PROVIDER: S-EPMC3764424 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature