PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes.

ABSTRACT: Proteolysis-targeting chimeras (PROTACs), which induce degradation by recruitment of an E3 ligase to a target protein, are gaining much interest as a new pharmacological modality. However, designing PROTACs is challenging. Formation of a ternary complex between the protein target, the PROTAC, and the recruited E3 ligase is considered paramount for successful degradation. A structural model of this ternary complex could in principle inform rational PROTAC design. Unfortunately, only a handful of structures are available for such complexes, necessitating tools for their modeling. We developed a combined protocol for the modeling of a ternary complex induced by a given PROTAC. Our protocol alternates between sampling of the protein-protein interaction space and the PROTAC molecule conformatio

SUBMITTER: Zaidman D 

PROVIDER: S-EPMC7592117 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature