Computational Insight Into the Small Molecule Intervening PD-L1 Dimerization and the Potential Structure-Activity Relationship.

ABSTRACT: Recently, small-molecule compounds have been reported to block the PD-1/PD-L1 interaction by inducing the dimerization of PD-L1. All these inhibitors had a common scaffold and interacted with the cavity formed by two PD-L1 monomers. This special interactive mode provided clues for the structure-based drug design, however, also showed limitations for the discovery of small-molecule inhibitors with new scaffolds. In this study, we revealed the structure-activity relationship of the current small-molecule inhibitors targeting dimerization of PD-L1 by predicting their binding and unbinding mechanism via conventional molecular dynamics and metadynamics simulation. During the binding process, the representative inhibitors (BMS-8 and BMS-1166) tended to have a more stable binding mode with one PD

SUBMITTER: Shi D 

PROVIDER: S-EPMC6861162 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature