Metadynamics is a popular enhanced sampling algorithm for computing the free energy
landscape of rare events by using molecular dynamics simulation. Ten years ago, Tiwary …

The application of computational approaches in drug discovery has been consolidated in
the last decades. These families of techniques are usually grouped under the common …

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 …

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 …

Lipids play important modulatory and structural roles for membrane proteins. Molecular
dynamics simulations are frequently used to provide insights into the nature of these protein …

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

Drug-target residence time (τ), one of the main determinants of drug efficacy, remains highly
challenging to predict computationally and, therefore, is usually not considered in the early …

ABSTRACT Background Protein-protein interactions (PPIs) are intriguing targets for
designing novel small-molecule inhibitors. The role of PPIs in various infectious and …

The dissociation rate (k off) associated with ligand unbinding events from proteins is a
parameter of fundamental importance in drug design. Here we review recent major …

Solvent organization is a key but underexploited contributor to the thermodynamics of
protein–ligand recognition, with implications for ligand discovery, drug resistance, and …