Drug–target residence time: Analyzing cooperativity effects in G protein-coupled receptors by mathematical modeling and molecular dynamics simulations

Abstract

Drug–target residence time (t) is reviewed from two perspectives: mathematics and molecular dynamics. The first focuses on the quantification of t using a mathematical formalism applicable to different pharmacological mechanistic conditions. This formalism is based on the concept of the smallest-modulus eigenvalue of a subsystem of interest, in which the global formation process has been eliminated. The second includes relevant studies of recent years to provide a structural explanation of t predictions. Special attention is paid to physically supported artificial intelligence methods. The main objective of this minireview is to promote a combined approach in which mathematics and physics work synergistically to describe the complexity associated with t in G protein-coupled receptors.

Peer Reviewed

Postprint (published version)