Highlights•Currently, develo** a market-approved drug costs a staggering $2.6 billion.•In
silico methods have become an important strategy for narrowing down on promising lead …

PDZ domains are abundant protein interaction modules that often recognize short amino
acid motifs at the C-termini of target proteins. They regulate multiple biological processes …

Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with
neutral guests illustrate that the release of high-energy water from the cavity of cucurbit [n] …

Appropriate tuning of binding selectivity is a primary objective in the discovery and
optimization of a compound on the path toward develo** a drug. The environment in …

Introduction Nowadays, it is widely accepted that water molecules play a key role in binding
a ligand to a molecular target. Neglecting water molecules in the process of molecular …

Predicting changes in protein binding affinity due to single amino acid mutations helps us
better understand the driving forces underlying protein-protein interactions and design …

The hydrophobic effect—a rationalization of the insolubility of nonpolar molecules in water—
is centrally important to biomolecular recognition. Despite extensive research devoted to the …

The Schrödinger software suite contains a broad array of computational chemistry and
molecular modeling tools that can be used to study the interaction of peptides with proteins …

The design of high-affinity and analyte-selective receptors operating in aqueous solutions is
an outstanding problem in supramolecular chemistry. Directing the focus toward the unique …

In this review, we begin by introducing the basic principles of kinetics and thermodynamics
of target–drug binding within the context of drug discovery. In addition, we present a meta …