Computational chemistry and structure-based design have traditionally been viewed as a
subset of tools that could aid acceleration of the drug discovery process, but were not …

Alchemical free energy calculations are a useful tool for predicting free energy differences
associated with the transfer of molecules from one environment to another. The hallmark of …

Predicting protein–ligand binding affinities and the associated thermodynamics of
biomolecular recognition is a primary objective of structure-based drug design. Alchemical …

Ligand binding affinity calculations based on molecular dynamics (MD) simulations and non-
physical (alchemical) thermodynamic cycles have shown great promise for structure-based …

Computational methods constitute efficient strategies for screening and optimizing potential
drug molecules. A critical factor in this process is the binding affinity between candidate …

Free-energy calculations have seen increased usage in structure-based drug design.
Despite the rising interest, automation of the complex calculations and subsequent analysis …

Molecular mechanics (MM) potentials have long been a workhorse of computational
chemistry. Leveraging accuracy and speed, these functional forms find use in a wide variety …

Abstract While Relative Binding Free Energy (RBFE) calculations have become a mainstay
in lead optimization programs, the computational expense of performing these calculations …

The goal of the present manuscript is to succinctly trace the key technological steps in the
evolution of alchemical free energy methods (AFEMs) from a purely theoretical construct to a …

Accurate prediction of the absolute or relative protein–ligand binding affinity is one of the
major tasks in computer-aided drug design projects, especially in the stage of lead …