The drug discovery process is a rocky path that is full of challenges, with the result that very
few candidates progress from hit compound to a commercially available product, often due …

Rigorous physics-based methods to calculate binding free energies of protein–ligand
complexes have become a valued component of structure-based drug design. Relative and …

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling
as a mechanism of human systemic autoimmune disease,,,,,–, evidence of lupus-causing …

In the hit identification stage of drug discovery, a diverse chemical space needs to be
explored to identify initial hits. Contrary to empirical scoring functions, absolute protein …

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 …

In the present work, we describe the extraction of a natural product namely 1, 4, 9, 9-
tetramethyloctahydro-4, 7-(epoxymethano) azulen-5 (1H)-one, and its structure was …

Computational techniques can speed up the identification of hits and accelerate the
development of candidate molecules for drug discovery. Among techniques for predicting …

Mechanosensitive PIEZO channels constitute potential pharmacological targets for multiple
clinical conditions, spurring the search for potent chemical PIEZO modulators. Among them …

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 …