Docking experiments

Structure preparation and docking experiments with SPORES/PLANTS
Structure preparation and docking experiments with SPORES/PLANTS

Thomas Exner
Douglas Connect

Protein-ligand docking is a useful tool to find new lead compounds and to get ideas of important interactions between the ligands and the target especially in the early drug design phases. Using virtual screening, a very large (virtual) database can be docked with almost negligible time and financial demand and the most prominent hits can then be tested experimentally. Besides a reasonable description of the interactions in the complex using state-of-the-art scoring functions, it has become evident that the preparation of the structures used in docking is of almost equivalent importance.

In this workshop, we will discuss criteria for generating an optimal screening library and how to perform the structure preparation using SPORES including the generation of different protonation states, tautomers, and stereoisomers. These will then be docked using the PLANTS software and the results will analyzed to find leads for experimental testing and further optimization by derivatization.

(1) ten Brink, T.; Exner, T. E. " pKa Based Protonation States and Microspecies for Protein-Ligand Docking", J.Comput.Aided Mol.Des. 24, 935-942 (2010).

(2) ten Brink, T.; Exner, T. E. "The Influence of Protonation States on Protein-Ligand Docking Results", J.Chem.Inf.Model. 49, 1525-1546 (2009).

(3) Korb, O.; ten Brink, T.; Fredrick Robin Devadoss V. Keil, M.; Exner, T. E. " Are predefined decoy sets of ligand poses able to quantify scoring function accuracy?", J.Comput.-Aided Mol. Design 26, 185-197 (2012).

(4) Korb, O.; Stützle, T.; Exner, T. E. "Empirical Scoring Functions for Advanced Protein-Ligand Docking with PLANTS", J.Chem.Inf Model. 49, 84–96 (2009).

(5) Korb, O.; Stützle, T.; Exner, T. E. "An ant colony optimization approach to flexible protein-ligand docking", Swarm Intell. 1, 115-134 (2007).