Exploring rigid-backbone protein docking in biologics discovery: a test using the DARPin scaffold.

ABSTRACT: Accurate protein-protein docking remains challenging, especially for artificial biologics not coevolved naturally against their protein targets, like antibodies and other engineered scaffolds. We previously developed ProPOSE, an exhaustive docker with full atomistic details, which delivers cutting-edge performance by allowing side-chain rearrangements upon docking. However, extensive protein backbone flexibility limits its practical applicability as indicated by unbound docking tests. To explore the usefulness of ProPOSE on systems with limited backbone flexibility, here we tested the engineered scaffold DARPin, which is characterized by its relatively rigid protein backbone. A prospective screening campaign was undertaken, in which sequence-diversified DARPins were docked and ranked again

SUBMITTER: Gaudreault F 

PROVIDER: S-EPMC10484509 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature