Molecular structure pharmacophores

These pharmacophore techniques are different in format from the traditional pharmacophore definitions. They can not be easily visualized and mapped to the molecular structures rather, they are encoded as keys or topological/topographical descriptors. Nonetheless, they capture the same idea as the classic pharmacophore concept. Furthermore, this formalism is quite useful in building quantitative predictive models that can be used to classify and predict biological activities. 

The peculiar features of the three arAR supermolecules were translated into pharmacophore hypotheses by means of Catalyst software (Figure 8.2, unpublished results). Catalyst treats molecular structures as templates placing chemical functions in 3D space to interact with the receptor. Molecular flexibility is taken into account by considering each compound as a collection of conformers representing different areas of the molecules conformational space within a given energy range. 

De Benedetti, P.G., Cocchi, M., Menziani, M.C. and Fanelli, F. (1993) Theoretical quantitative structure-activity analysis and pharmacophore modelling of selective non congeneric ala-adrenergic antagonists. Journal of Molecular Structure (Theochem), 280, 283-290. 

Gund, P., Wipke, W.T., Iangridge, R. Computer searching of a molecular structure file for pharmacophoric patterns. Comput. Chem. Res. Educ. Technol. 1974, 3, 5-21. 

The understanding of three-dimensional molecular structure and the explanation of ligand-site affinity on hand of shape and functional group complementarity ( lock and key hypothesis) naturally lead to the introduction of the pharmacophore concept in medicinal chemistry and implicitly in computational chemistry see [6] and references therein. The specific physicochemical mechanisms controlling the macromolecule-ligand interactions could be, in principle, understood on a purely... 

Van drie, J.H., Weininger, D., and Martin, Y.C. ALADDIN an integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of three-dimensional molecular structures./. Comput.-Aided Mol. Des. 1998, 3, 225-251. 

Keywords Microtubule targeting agents, Molecular docking, Molecular modeling, Pharmacophore, Quantitative structure-activity relationships, Tubulin... 

Molecular descriptors and chemical spaces. The majority of chemoinformatics methods depend on the generation of chemical reference spaces into which molecular data sets are projected and where analysis or design is carried out. The definition of chemical spaces critically depends on the use of computational descriptors of molecular structure, physical or chemical properties, or pharmacophores. Essentially, any comparison of molecular characteristics that goes beyond simple structural comparison requires the calculation of property values and the application... 

Figure 4.1 Ligand-based virtual screening methods. The figure shows different computational methods for screening compound databases that take either a local or a global view on molecular structure. Molecular similarity methods that operate on molecular descriptors, histogram representations, superposition or (reduced) molecular graphs evaluate molecular structure globally. By contrast, local structural features are explored by substructure and pharmacophore searching or QSAR modeling.

The main factor that governs the transport of a compound by an active carrier system is the interaction of this compound with a carrier protein. In this case the description of the molecular structure should be similar to that used in ligand-based design to describe the interaction of the compound with any other protein using pharmacophoric representation or 3D-QSAR. 

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