Alignment docking-based

Constantino et al. used the combination of a docking-based alignment and 3D QSAR analysis to build a predictive model for 46 poly(ADP-ribose)polymer-ase (PARP) inhibitors [67]. Representative PARP inhibitors were docked into... 

Alignment of 202 artemisinin analogs based on docking to hemin. 

Figure 10. Alignment of 202 artemisinin analogues based on proposed docking (to hemin) conformation.

Virtual screening often benefits from an expert bias which helps focus on more desirable results, given in the form of additional information. A point in case is docking under pharmacophore constraints [37] or the concept of relative pharmacophores with a special internal reference point [38]. Yet another application for a directionally biased compound comparison is the selection of chemical reagents where functional attachment points are aligned and pharmacopho-ric features are examined relative to this point of reference by a procedure termed GaP [39]. Other concepts which try to describe combinatorial products in terms of their educts and need a special reference point are shape-based To-pomers [24] and pharmacophore based OsPreys [40]. 

Fig. 11.3 Receptor-based alignment of all investigated inhibitors as obtained by the docking analysis. The solvent-accessible surface of the binding pocket is displayed.

The ligand-based alignments were carried out using the superposition program FlexS [2], and compound 4j as rigid template (in the conformation obtained by the docking) on the one site and the Multifit routine within the SYBYL software and the same template on the other site (Fig. 11.5). 

Zhou, Z., Madura, J.D. 3D QSAR Analysis of HIV-1 RT Nonnucleoside Inhibitors, TIBO Derivatives Based on Docking Conformation and Alignment. /. Chem. Inf Comput. Sci. 2004, 44, 2167-2178. 

Deoxythymidine monophosphate derivatives that inhibit thymidine monophosphate kinase 36 MFA Alignments performed with least-squares (predictive R2=0.70), pharmacophore (0.56), or docked conformations (0.72). Receptor-based alignment performed best Aparna et al. (42)... 

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