Sampling of structure and sequence space of small protein folds.

ABSTRACT: Nature only samples a small fraction of the sequence space that can fold into stable proteins. Furthermore, small structural variations in a single fold, sometimes only a few amino acids, can define a protein's molecular function. Hence, to design proteins with novel functionalities, such as molecular recognition, methods to control and sample shape diversity are necessary. To explore this space, we developed and experimentally validated a computational platform that can design a wide variety of small protein folds while sampling shape diversity. We designed and evaluated stability of about 30,000 de novo protein designs of eight different folds. Among these designs, about 6,200 stable proteins were identified, including some predicted to have a first-of-its-kind minimalized thioredoxin fo

SUBMITTER: Linsky TW 

PROVIDER: S-EPMC9684540 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature