Assessing and enhancing foldability in designed proteins.

ABSTRACT: Recent advances in protein-design methodology have led to a dramatic increase in reliability and scale. With these advances, dozens and even thousands of designed proteins are automatically generated and screened. Nevertheless, the success rate, particularly in design of functional proteins, is low and fundamental goals such as reliable de novo design of efficient enzymes remain beyond reach. Experimental analyses have consistently indicated that a major reason for design failure is inaccuracy and misfolding relative to the design conception. To address this challenge, we describe complementary methods to diagnose and ameliorate suboptimal regions in designed proteins: first, we develop a Rosetta atomistic computational mutation scanning approach to detect energetically suboptimal position

SUBMITTER: Listov D 

PROVIDER: S-EPMC9375437 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature