Shape signatures

Zauhar, R. J. and Welsh, W. J. (2000) Application of the shape signatures approach to ligand-and-receptor based drug design. Abstracts of Papers of the American Chemical Society 220, 70-COMP, Part 1. 

The basic idea of alignment-free shape matching is that a set of rotation- and translation-free descriptors are calculated for con-formers under consideration, and then some similarity measure is devised to quantify the similarity between two molecular objects. Zauhar s shape signatures (45), Breneman s PEST and PESD methods (54-56), the USR (ultrafast shape recognition) method... 

The PEST and PESD Method These methods were developed by Breneman s group. The PEST (property-encoded surface translator) method is based on the combination of the TAE descriptors (54) and the shape signatures idea by Zauhar... 

Nagarajan, K., Zauhar, R., Welsh, W. J. (2005) Enrichment of ligands for the serotonin receptor using the shape signatures approach. J Chem Inf Model 45, 49-57. 

A new method, shape signatures, in the area of computer-aided molecular design has been studied <2003JME5674>. The method has been demonstrated to work well in selecting molecules on the basis of shape and polarity and has been applied to a receptor-based strategy. Dibenzo[ /]thiepine appears in the hit list for 57/-benz[ /]azepin. 

A plot of log A versus log n gives a straight line with a slope of -s, wWch is the shape signature of the particle, (generalizations of this method to three-dimensional particles are also possible. Particle shapes can be analyzed and reproduced using this Fourier transform method. 

A shape analysis of NUPCO s provides a formal "shape signature" of the collective properties of the nuclear arrangement K. Of course, NUPCO s are common for all electronic states of the same nuclear arrangement. Consequently, NUPCO s are not suitable to account for the shape differences between various electronically excited states of molecules, especially in formal "vertical" excitations. However, electronic excitations are often accompanied by changes of the optimum nuclear arrangement K, and NUPCO s can be used for an approximate description of these contributions to the overall shape changes caused by the electronic excitations. 

Active/Inactive Assignment. . Structural alerts Pharmacophores Decision Tree (or Decision Forest) Shape Signatures... 

We now introduce a new informatics tool called Shape Signatures that shows promise for drug discovery and computational toxicology. In contrast to QSAR and other descriptor-based approaches that compute hundreds of discrete descriptors for each molecule, the Shape Signature can be viewed as a very compact descriptor that encodes molecular shape and electrostatics in a single entity [76-78]. 

Shape Signatures have been shown to have utility for rapid screening and prioritizing of potential hazardous chemicals. For example, Shape Signatures... 

Figure 6.13 Key steps in generation 1-dimensional (ID) shape signature for 17P-estradiol.

Figure 6.14 Snapshot of Shape Signatures database of PDB-extracted ligands.

Figure 6.15 Depiction of the process by which a query molecule is used to search the PDB-based Shape Signatures database to discern potential protein targets and biological mechanisms.

Meek PJ, Liu Z, Tian L, Wang CY, Welsh WJ, Zauhar RJ. Shape signatures Speeding up computer aided drug discovery. Drug Discov Today 2006 11 895-904. 

Zauhar RJ, Moyna G, Tian L, Li Z, Welsh WJ. Shape signatures A new approach to computer-aided ligand- and receptor-based drug design. J Med Chem 2003 46 5674-90. 

Zauhar, R.J., Moyna, G., Xian, L, Li, Z., and Welsh, W.J. (2003) Shape signatures, a new approach to computer-aided ligand-and receptor-based drug design. Journal of Medicinal Chemistry, 46, 5674—5690. 

Zhang, D. and Lu, G., A comparative study on shape retrieval using Fourier descriptors with different shape signatures , pp. 1— 9... 

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