Molecular overlay

Jones G, P Willett and R C Glen 1995a. A Genetic Algorithm for Flexible Molecular Overlay an Pharmacophore Elucidation. Journal of Computer-Aided Molecular Design 9 532-549. 

The molecular overlay experiment orients the molecules to hnd the best RMS or held ht. The held ht is based on electrostatic and steric interactions. The application can hnd either the best total alignment of all molecules or the best match of all molecules to a specihed target molecule. Alignment can include a database search for conformers that show the best alignment based on the molecules under study. 

Jones G, Willett P, Glen RC. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation. / Comput Aided Mol Des 1995 9(6) 532-49. 

Natarajan, R., Basak, S. C., Balaban, A. T., Klun, J. A., Schmidt, W. F. Chirality index, molecular overlay and biological activity of diastereoisomeric mosquito repellents. Pest. Manag. Sci. 2005, 61, 1193-1201. 

Basak, S. C., Natarajan, R., Nowak, W., Miszta, P., Klun, J. A. Three dimensional structure-activity relationships (3D-QSAR) for insect repellency of diastereoisomeric compounds A hierarchical molecular overlay approach. SAR QSAR Environ. Res. 2007,18, 237-250. 

Algorithm for Flexible Molecular Overlay and Pharmacophore Elucidation. 

Molecular superimposition is the most critical step in any CoMFA study and it was therefore thoroughly studied by testing several different alignments. Benazoline was chosen as the template, since it is the most active ligand and has a relatively limited conformational mobility. Its lowest minimum energy conformer, in which the inter-ring torsion angle between naphtyl and imidazoline moieties is -32.3, was selected for the different molecular overlays. 

A variety of QSAR models have also been investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) [91, 92] models have been used for the substrate-based and keto acid inhibitors (represented by compounds 27 and 30). Molecular overlays were initially developed for each class, and by comparison of activity data with these overlays, a model can be developed to take into account both steric and electrostatic fields around the inhibitors this is illustrated in Fig. 5 [91]. 

Jones, G., Willett, P., and Glen, R.C. (1995) A genetic algorithm for fiexible molecular overlay and pharmacophore elucidation. Journal of Computer-Aided Molecular Design, 9, 532-549. 

These techniques often involve statistical treatment of data in a largely retrospective manner which is further limited by the arbitrary choice of common substructures, pharmacophores, binding points, and molecular overlays. In classical QSAR the limitations can be quite severe in that regressions are confined to a series of closely related structures often differing in relatively minor ways. More recent innovations Involve molecular shape analysis (13) and distance geometry methods (14). These techniques represent significant steps toward a true three-dimensional SAR with some predictive... 

A molecular overlay was generated in which the N-benzyl and carboxy groups of the Takeda compound corresponded to the Tyr-4 side chain and the... 

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