Development of Successful Methods for Induced-Fit Docking

In the last few years there have been a number of success stories published describing methods for incorporating induced fit in ligand docking using ICM-Pro. Including using multiple receptor conformations in ligand docking and virtual screening (Totrov and Abagyan 2008, Bottegoni et al 2009) and methods to allow the ligand in the binding pocket guide the conformation of the receptor (e.g. Bisson et al 2007, Cavasotto et al 2008 and Katrtich et al 2010). Other methods that have been developed using ICM include normal mode approaches (Rueda et al 2009), an approach using dual alanine scanning and refinement ( SCARE - Bottegoni et al 2009) and a method designed for modeling kinases called DOLPHIN (Kufareva et al 2009).

References

Totrov M, Abagyan R. Flexible ligand docking to multiple receptor conformations: a practical alternative. Curr. Opin. Struct. Biol 2008 Apr;18(2):178-184.

Bottegoni G, Kufareva I, Totrov M, Abagyan R. A new method for ligand docking to flexible receptors by dual alanine scanning and refinement (SCARE). J. Comput. Aided Mol. Des 2008 May;22(5):311-325.

Rueda M, Bottegoni G, Abagyan R. Recipes for the selection of experimental protein conformations for virtual screening. J Chem Inf Model. 2010 Jan;50(1):186-93.

Rueda M, Bottegoni G, Abagyan R. Consistent improvement of cross-docking results using binding site ensembles generated with elastic network normal modes. J Chem Inf Model 2009 Mar;49(3):716-725.

Katritch V, Rueda M, Lam PC, Yeager M, Abagyan R. GPCR 3D homology models for ligand screening: lessons learned from blind predictions of adenosine A2a receptor complex. Proteins. 2010 Jan;78(1):197-211.

Kufareva I, Abagyan R. Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states. J. Med. Chem 2008 Dec;51(24):7921-7932.

Cavasotto, C.N. and Abagyan, R.A. Protein Flexibility in Ligand Docking and Virtual Screening To Protein Kinase s J. Mol. Biol. Mar 12; 337(1): 209-25

Cavasotto CN, Orry AJ, Murgolo NJ, Czarniecki MF, Kocsi SA, Hawes BE, O'Neill KA, Hine H, Burton MS, Voigt JH, Abagyan RA, Bayne ML, Monsma FJ Jr. Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Stru cture-Based Virtual Screening. J Med Chem. 2008 Feb 14;51(3):581-8.

Cavasotto, C., Orry, A.J.W., and Abagyan, R.A. Structure-Based Identification of Binding Sites, Native Ligands and Potential Inhibitors for G-Protein Coupled Receptors Proteins: Structure, Function, and Genetics 51(3), 423-433