Docking Approaches

Fleksy [102] is a docking protocol that incorporates the FlexE docking [53] engine already described in Section 8.2.1.2. Given an experimental input structure, the protocol generates multiple receptor conformations to introduce receptor flexibility. For rule-based identified or alternatively user-defined residues, it extracts some most 

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Forino M, Jung D, Easton JB, Houghton PJ, Pellecchia M. Virtual docking approaches to protein kinase B inhibition. J Med Chem 2005 48 2278-81. 

Dominguez, C., et al.. Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches. Structure (Camb), 2004, 12(4), 633—44. 

Docking simulation is distinct from wet laboratory chemistry, where chemical reactions are performed using real rather than virtual compounds. The docking approach is more cost effective and efficient than the conventional chemical synthesis route. It allows a large database of virtual compounds to be screened and matched up with the binding site of the targeted protein. 

Fig. 8.1. Schematic depiction of the seed and grow docking approach for structure-based library design. The programs that use this approach include CombiDOCK and PR0 SELECT.

Fig. 8.2. Schematic depiction of the dock and link docking approach. The program BUILDER v.2 is based on this approach.

Kua J, Zhang Y, McCammon JA (2002) Studying enzyme binding specificity in acetylcholinesterase using a combined molecular dynamics and multiple docking approach. J Am Chem Soc 124(28) 8260-8267... 

Throughout this chapter, we roughly separate docking approaches by their treatment of protein flexibility. Within the two broad categories (rigid body and flexible docking), the docking problem can be separated into two subproblems ... 

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