Journal de médecine pulmonaire

Molecular Dynamics at the Checkpoint

Bernhard Roither, Chris Oostenbrink, Georg Pfeiler, Heinz Koelbl and Wolfgang Schreiner*

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.