Predicting a Kind of Unusual Multiple-States Dimerization-Modes Transformation in Protein PD-L1 System by Computational Investigation and a Generalized Rate Theory

Abstract

The new cancer immunotherapy has been carried out with an almost messianic zeal, but its molecular basis remains unclear due to the complexity of programmed death ligand 1 (PD-L1) dimerization. In this study, a new and integral multiple dimerization-modes transformation process of PD-L1s (with a new PD-L1 dimerization mode and a new transformation path discovered) and the corresponding mechanism are predicted using theoretical and computational methods. The results of the state analysis show that 5 stable binding states exist in system. A generalized inter-state transformation rate (GITR) theory is also proposed in such multiple-states self-assembly system to explore the kinetic characteristics of inter-state transformation. A “drug insertion” path was identified as the dominant path of the PD-L1 dimerization-modes transformation. Above results can provide supports for both the relative drug design and other multiple-states self-assembly system from the theoretical chemistry perspective.