Fully flexible docking

Figure 8.3 Summary of methods for fully flexible docking.

Fully flexible docking methods are a step toward more reliable compound assessment. For their application in structure-based virtual screening, some effects... 

Efficiency of Fully Flexible Docking Approaches in Retrospective... 

Approaches for fully flexible docking either follow a conformational selection or an induced fit concept (Figure 8.3). Ensemble docking implements the principle of conformational selection and relies on the protein structural change occurring before the ligand binds to the protein. The ensemble of input protein conformations... 

Kazemi, S., Kruger, D.M., Siroddn, F., and Gohlke, H. (2009) Elastic potential grids accurate and efficient representation of intermolecular interactions for fully flexible docking. ChemMedChem, 4 (8), 1264-1268. 

IV, ] Ruppert and A N Jain 1996. Hammerhead Fast, Fully Automated Docking of Flexible ands to Protein Binding Sites. Chemistry and Biology 3 449-462. 

Welch, W., Ruppert, J., and Jain, A.N. Hammerhead fast, fully automated docking of flexible ligands to protein binding sites. Chem. Biol. 1996, 3, 449-462. 

Gehlhaar, D. K., Bouzida, D., Rejto, P. A. (1998) Fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases. Proceedings of the 7th International Conference on Evolutionary Programming, MIT Press, Cambridge, MA., pp. 449-461. 

Welch, W., J. Ruppert, and A. N. Jain. 1996. Hammerhead Last, fully automated docking of flexible ligands into protein binding sites. J Chem Biol 3 419-62. 

Fernandez-Recio J. ICM-DISCO docking by global energy optimization with fully flexible side chains. Proteins 2003 52 113-117. 

Jain AN (2003) Surflex fully automatic flexible molecular docking using a molecular similarity-based search engine. J Med Chem 46 499-511... 

Jain A N (2003). Surflex Fully automatic flexible molecular docking nsing a molecnlar similarity-based search engine. J. Med. Chem. 46 499-511. 

An additional problem with crystal structures that can give rise to a misleading model is the thermal motion and disorder within the crystalline lattice. Local regions of electron density can be poorly defined, even for structures with relatively good resolution if, for example, a protein residue is labile in the crystalline state. If undetected, a residue can be poorly modeled, misassigned, or omitted from the model. Even when detected and fully modeled, disorder implies flexibility, which may need specific handling in a docking study. 

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