Since its inception nearly a half century ago, CHARMM has been playing a central role in
computational biochemistry and biophysics. Commensurate with the developments in …

This Perspective provides a contextual explanation of the current state-of-the-art alchemical
free energy methods and their role in drug discovery as well as highlights select emerging …

We present an alchemical enhanced sampling (ACES) method implemented in the GPU-
accelerated AMBER free energy MD engine. The methods hinges on the creation of an …

We develop a framework for the design of optimized alchemical transformation pathways in
free energy simulations using nonlinear mixing and a new functional form for so-called …

Alchemical absolute binding free energy (ABFE) calculations have substantial potential in
drug discovery, but are often prohibitively computationally expensive. To unlock their …

The grand challenge in structure-based drug design is achieving accurate prediction of
binding free energies. Molecular dynamics (MD) simulations enable modeling of …

An alchemical enhanced sampling (ACES) method has recently been introduced to facilitate
importance sampling in free energy simulations. The method achieves enhanced sampling …

Relative binding free energy (RBFE) calculations have emerged as a powerful tool that
supports ligand optimization in drug discovery. Despite many successes, the use of RBFEs …

Alchemical free energy calculations generally require intermediate states along a coupling
parameter λ to establish sufficient phase space overlap for obtaining converged results …

The calculation of relative free-energy differences between different compounds plays an
important role in drug design to identify potent binders for a given protein target. Most …