Automated generation of pharmacophore

Although pharmacophore mapping can be completed manually in simple and straightforward cases, most of the applications require the automated generation of pharmacophore. There are several software suites available for this purpose. HipHop and Hypo-Gen are both featured by the Catalyst package. ... 

Figure 3 Structural alignments with discrete properties. Methods are based on discrete properties using the DG algorithm (1) or clique-detection (11) as implemented in distance comparisons (DISCO), and Apex-3D. The structure representation, based on discrete properties, resorts to one atomic descriptor (I), usually the atom type, or multiple atomic or site descriptors (II). In the first method (I), the conformational analysis is restricted to the generation of molecular geometries which allow a common arrangement of selected phaimacophoric moieties present in a rigid compound used as template. In the second method (II), the conformational analysis procedure may involve a systematic enumeration of all the possible conformadons for each ligand. The search similarity is directed towards the confirmation of a predefined pharmacophore postulated by the modeler or from some classical SAR in the case of the active analog approach (1), or the automated identification of pharmacophores and bioacdve conformations (II)...

Inductive Inference Module Performs generation of rules on the basis of structure and activity data based on algorithms of the logical structural approach [20] and provides tools for automated selection of biophores (pharmacophores) and interactive building of 3D QSAR models. The module performs statistical evaluation of the predictive and discriminating power of selected biophores and models. 

After ALADDIN, this author and Martin parted ways, but each played a role in the rise of two distinct pharmacophore discovery methods. In 1990, this author joined, as a founding member and first scientist, a new company in Silicon Valley, BioCAD, dedicated to the development of software to assist drug discovery. Our software, Catalyst, contained three components conformational analysis, 3D database searching, and Hypothesis Generation —a novel approach to pharmacophore discovery. Catalyst represented the first fully automated method for pharmacophore discovery. 

Li H, Sutter J, Hoffmann R. HypoGen an automated system for generating 3D predictive pharmacophore models. In Gtiner OF, editor. Pharmacophore perception, development and use in drug design., La Jolla International University Line, 2000. p. 173-89. 

Currently, there is no automated tool in MOE that can generate pharmacophore models from a set of active/inactive molecules. As a consequence, there is no pharmacophore scoring or ranking or a validation method implemented in the program. 

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