Statistical thermodynamic basis in drug-receptor interactions: double annihilation and double decoupling alchemical theories, revisited

TL;DR

This paper revisits the statistical mechanics foundation of alchemical methods in drug-receptor interactions, unifying various approaches and discussing their connections within nonequilibrium thermodynamics.

Contribution

It provides a comprehensive theoretical review that unifies key alchemical methods in drug-receptor interaction studies, highlighting their differences and broader thermodynamic context.

Findings

Unified treatment of alchemical approaches

Clarified connections between different methods

Placed methods within nonequilibrium thermodynamics

Abstract

Alchemical theory is emerging as a promising tool in the context of molecular dynamics simulations for drug discovery projects. In this theoretical contribution, I revisit the statistical mechanics foundation of non covalent interactions in drug-receptor systems, providing a unifying treatment that encompasses the most important variants in the alchemical approaches, from the seminal Double Annihilation Method by Jorgensen and Ravimohan [W.L. Jorgensen and C. Ravimohan, J. Chem. Phys. 83,3050, 1985], to the Gilson's Double Decoupling Method [M. K. Gilson and J. A. Given and B. L. Bush and J. A. McCammon, Biophys. J. 72, 1047 1997] and the Deng and Roux alchemical theory [Y. Deng and B. Roux, J. Chem. Theory Comput., 2, 1255 2006]. Connections and differences between the various alchemical approaches are highlighted and discussed, and finally placed into the broader context of nonequilibrium thermodynamics.