Reviews in Computational Chemistry Volume 18

N
Scoring Functions for Receptor–Ligand Interactions 49
solvated receptor
binding site
O
solvated receptor-ligand complex
N
HO
O
solvated ensemble
of ligand conformations
hydrogen bond
hydrophobic contacts
charge-assisted hydrogen bond
Figure 3 Overview of the receptor–ligand binding process. All species involved are
solvated by water (symbolized by gray spheres). The binding free energy difference
between the bound and unbound state is a sum of enthalpic components (breaking and
formation of hydrogen bonds, formation of specific hydrophobic contacts), and entropic
components (release of water from hydrophobic surfaces to solvent, loss of
conformational mobility of receptor and ligand).
DESCRIPTION OF SCORING FUNCTIONS FOR
RECEPTOR–LIGAND INTERACTIONS
A rigorous theoretical treatment of reversible receptor–ligand binding
requires full consideration of all species involved in the binding equilibrium.
In the unbound state, both the ligand and the receptor are separately solvated
and do not interact. In the bound state, both partners are partially desolvated
and form interactions with each other. Since it is the free energy of binding one
is interested in determining, the energies of the solvated receptor, the solvated
ligand, and the solvated complex should be calculated as ensemble averages.
O
HO
O