Peptide design by optimization on a data-parameterized protein interaction landscape.

ABSTRACT: Many applications in protein engineering require optimizing multiple protein properties simultaneously, such as binding one target but not others or binding a target while maintaining stability. Such multistate design problems require navigating a high-dimensional space to find proteins with desired characteristics. A model that relates protein sequence to functional attributes can guide design to solutions that would be hard to discover via screening. In this work, we measured thousands of protein-peptide binding affinities with the high-throughput interaction assay amped SORTCERY and used the data to parameterize a model of the alpha-helical peptide-binding landscape for three members of the Bcl-2 family of proteins: Bcl-x_L, Mcl-1, and Bfl-1. We applied optimization protocols

SUBMITTER: Jenson JM 

PROVIDER: S-EPMC6217393 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature