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 …

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

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

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 …

The Alchemical Transfer Method (ATM) is herein validated against the relative binding-free
energies (RBFEs) of a diverse set of protein–ligand complexes. We employed a streamlined …

CRISPR-Cas12a is a powerful RNA-guided genome-editing system that generates double-
strand DNA breaks using its single RuvC nuclease domain by a sequential mechanism in …

We report an automated workflow for production free-energy simulation setup and analysis
(ProFESSA) using the GPU-accelerated AMBER free-energy engine with enhanced …

We present software infrastructure for the design and testing of new quantum
mechanical/molecular mechanical and machine-learning potential (QM/MM− ΔMLP) force …

RNA molecules play a vital role in biological processes within the cell, with significant
implications for science and medicine. Notably, the biological functions exerted by specific …