ABSTRACT
Solvent effects play a fundamental role in mediating the affinity of small molecules for protein binding sites. For instance, it is well known that water has the ability to severely dampen intermolecular electrostatic interactions, to reduce affinities by solvating polar or charged groups, and to contribute to binding through the hydrophobic effect. Given the significance of this role, it is essential that these effects be considered when computationally evaluating protein-ligand complexes. However, because these effects are notoriously difficult and often time-consuming to evaluate, they are frequently neglected when computational speed is an issue; this is especially true for high throughput docking (HTD) studies.
