Flexible Ligand Docking

Docking flexible ligands to macromolecular receptors by molecular shape, J. Med. 

Dixon, J.S., Kuntz, I.D., and Venkataraghavan, R. Docking flexible ligands to macromolecular receptors by molecular shape./. Med. Chem. 1986,... 

Kramer, B., Rarey, M., Lengauer, T. (1997) CASP2 experiences with docking flexible ligands using FlexX. Proteins Suppl 1, 221-225. 

CASP2 Experiences with Docking Flexible Ligands Using FlexX. 

Chem., 29, 2149 (1986). Docking Flexible Ligands to Macromolecular Receptors by Molecular Shape. 

B. Kramer, M. Rarey, and T. Lengauer. Casp-2 experiences with docking flexible ligands using flexx. PROTEINS ... 

Zhao, Y. and Sanner, M.F. (2007) FLIPDock docking flexible ligands into flexible receptors. Proteins, 68, 726-737. 

As discussed above, side-chain movement or protein flexibility plays an important role in a docking process. Usually, uncertainly in side-chain placement or loop modelhng arises in protein stmctures predicted through homology modelling. Only a few docking tools consider these, like FlexE. This is a tool which considers the protein structure variations or flexibility to dock flexible ligands [22] (Fig. 4.51). 

Because rigid pharmacophoric searching is based on the positions of explicit atoms or points, it is often difficult to pose queries based on directed vectors in space. A specialized search system, CAVEAT, has been developed that permits the specification of queries based on the relative orientation and position of bond vectors in space. If the query bond vectors have been derived from a docked flexible ligand, then when a database of rigid ring-systems (CAST-3D or CSD) is searched, CAVEAT will identify potential substructural skeletons which could act as a rigid mimic of the core substructure of the ligand. 

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