Molecular Dynamics at the Checkpoint

Computational molecular dynamics and by big data analysis disclose molecular movement patterns relevant for drug development and function. Atoms in the contact zones of the PD-1 receptor move differently depending on the binding partner: the natural ligand, PD-L1, or the checkpoint inhibitors nivolumab and pembrolizumab, respectively. Computational analysis was performed by an interdisciplinary team from MedUni Vienna and the University of Natural Resources, Vienna. The natural ligand, PD-L1, not only binds but also activates PD-1, thereby inducing T-cell apoptosis. Cancer cells may, by expressing PD-L1, halt natural immune attack and thus survive. Checkpoint inhibitors are designed to just bind to PD-1, but without activating it. This functional difference is reflected by molecular movements analyzed in the papers by Roither being outlined here.