One of the most important biological processes at the molecular level is the formation of
protein–ligand complexes. Therefore, determining their structure and underlying key …

Rigorous binding free energy methods in drug discovery are growing in popularity because
of a combination of methodological advances, improvements in computer hardware, and …

Simulations of molecular dynamics (MD) are playing an increasingly important role in
structure-based drug discovery (SBDD). Here we review the use of MD for proteins in …

The prediction of protein–ligand binding affinities is of central interest in computer-aided
drug discovery, but it is still difficult to achieve a high degree of accuracy. Recent studies …

Highlights•Mixed solvent dynamics can characterise what will bind to a site on a
protein.•Dynamic docking approaches can allow for protein flexibility in ligand …

Drug molecules adopt a range of conformations both in solution and in their protein-bound
state. The strain and reduced flexibility of bound drugs can partially counter the …

The presence of water molecules plays an important role in the accuracy of ligand− protein
docking predictions. Comprehensive docking simulations have been performed on a large …

Structure-based virtual screening relies on classical scoring functions that often fail to
reliably discriminate binders from nonbinders. In this work, we present a high-throughput …

Improving the capability of atomistic computer models to predict the thermodynamics of
noncovalent binding is critical for successful structure-based drug design, and the accuracy …

Binding sites present well-defined interaction patterns that putative ligands must meet.
Knowing them is essential to guide structure-based drug discovery projects. However …