Abstract:
Molecular docking methodology explores the behavior
of small molecules in the binding site of a target protein.
As more protein structures are determined experimentally
using X-ray crystallography or nuclear magnetic resonance
(NMR) spectroscopy, molecular docking is increasingly used
as a tool in drug discovery. Docking against homologymodeled
targets also becomes possible for proteins whose
structures are not known. With the docking strategies, the
druggability of the compounds and their specificity against a
particular target can be calculated for further lead optimization
processes. Molecular docking programs perform a search algorithm
in which the conformation of the ligand is evaluated
recursively until the convergence to the minimum energy is
reached. Finally, an affinity scoring function, ΔG [U total in
kcal/mol], is employed to rank the candidate poses as the sum
of the electrostatic and van der Waals energies. The driving
forces for these specific interactions in biological systems aim
toward complementarities between the shape and electrostatics
of the binding site surfaces and the ligand or substrate.
