Descriptor pharmacophores

Quantitative Structure-Activity Relationship models are used increasingly in chemical data mining and combinatorial library design [5, 6]. For example, three-dimensional (3-D) stereoelectronic pharmacophore based on QSAR modeling was used recently to search the National Cancer Institute Repository of Small Molecules [7] to find new leads for inhibiting HIV type 1 reverse transcriptase at the nonnucleoside binding site [8]. A descriptor pharmacophore concept was introduced by us recently [9] on the basis of variable selection QSAR the descriptor pharmacophore is defined as a subset of... 

Teopsha, A. Zheng, W. Identification of the descriptor pharmacophores using variable selection QSAR applications to database mining. Curr. Pharm. Des. 2001, 7, 599-612. 

Often, all alignment-based methods and molecular field and potential calculations are classified as pharmacophore perception techniques. We will include most of these methods in this review however, when using the term pharmacophore model, we will be referring mainly to one specific type of perception, namely three-dimensional feature-based pharmacophore models represented by geometry or location constraints, qualitative or quantitative. An extrapolation of the pharmacophore approach to a set of multi-dimensional descriptors (pharmacophore fingerprints) has been developed mostly for library design and focusing purposes [3-8]. 

MOE/QuaSAR Chemical Computing Group Inc. www.chemcomp.com/fdept/prodinfo.htm 2D (physical properties, subdivided surface areas, atom and bond counts, connectivity indices, adjacency and distance matrix descriptors, pharmacophore feature, partial charge descriptors), and 3D descriptors... 

The Descriptor Pharmacophore Concept and Variable Selection QSAR, 60... 

This consideration emphasizes the analogy between pharmacophore identification and variable selection QSAR. On the basis of this analogy, we now expand the notion of chemical pharmacophoreto that of the more general descriptor pharmacophore. We shall define descriptor pharmacophore as a special subset of molecular descriptors (of any nature, not only chemical functional groups) optimized in the process of variable selection QSAR, to achieve the most significant correlation between descriptor values and biological activity. 

In summary, each parent in this method represents a QSAR equation with randomly chosen variables, and the purpose of the calculation is to evolve from the initial population of the QSAR equations to the population with the highest average value of the fitness function. In the course of the GA-PLS process, the initial number of members of the population (100) is maintained while the average value of the fitness function for the whole population converges to a high number. The best model is characterized by the highest value of the fitness function as well as by specific descriptor selection (descriptor pharmacophore) that affords such a model. 

Select a subset of n descriptors randomly in is a number between 1 and the total number of available descriptors) as a hypothetical descriptor pharmacophore (HDP). 

ChemDiverse pharmacophore descriptors substructure descriptors ( pharmacophore-... 

PDQ descriptors = Pharmacophore-Derived Query descriptors —> substructure descriptors (0 pharmacophore-based descriptors)... 

PharmPrint descriptors substructure descriptors ( pharmacophore-based descriptors) phase capacity ratio = capacity factor —> chromatographic descriptors... 

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