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Drug-target residence time: Analyzing cooperativity effects in G protein-coupled receptors by mathematical modeling
Antonio J Ortiz1, Antoniel A S Gomes1, Pedro Renault1
1Laboratory of Molecular Neuropharmacology and Bioinformatics, Unitat de Bioestadística and Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain; Unitat de Neurociència Traslacional, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT), Institut de Neurociències, Universitat Autònoma de Barcelona, Spain.
Abstract:
Drug-target residence time (τ) is reviewed from two perspectives: mathematics and molecular dynamics. The first focuses on the quantification of τ 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 τ 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 τ in G protein-coupled receptors.
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