Pharmacophore conformational analysis

G. Melacini, Q. Zhu, G. Osapay, M. Goodman, A Refined Model for the Somatostatin Pharmacophore Conformational Analysis of Lanthionine-Sandostatin Analogs , J. Med. Chem. 1997, 40, 2252-2258. 

DM Mottola, S Laiter, VJ Watts, A Tropsha, SW Wyrick, DE Nichols, P Mailman. Conformational analysis of d dopamine receptor agonists Pharmacophore assessment and receptor mapping. J Med Chem 39 285-296, 1996. 

Knust H, Hoffmann RW (2003) Synthesis and Conformational Analysis of Macrocyclic Dilactones Mimicking the Pharmacophore of Aplysiatoxin. Helv Chim Acta 86 1871... 

The relatively high conformational flexibility of many drug molecules requires that an effective conformational sampling is performed for a pharmacophore-based analysis. The method used in ChemDiverse is based on an explicit "on-the-fly" generation of conformers done at search time. A conformation is accepted or rejected based on a fast evaluation of steric... 

Rein, K.S., Baden, D.G., and Gawley, R.E. 1994. Conformational analysis of the sodium-channel modulator brevetoxin-A, comparison with brevetoxin-B conformations, and a hypothesis about the common pharmacophore of the site-5 toxins. Journal of Organic Chemistry 59, 2101-2106. 

P-glycoprotein (P-gp) substrate predictions are evaluated using Almond 3.2, a pharmacophore pattern analysis software that combines MIF distances with energies [27], using a model initially derived from P-gp ATP-ase activity [28]. The model contains about 100 drugs (60 known substrates, and 40 nonbinders), each evaluated over 100 diverse conformations (G. Cruciani, personal communication). 

Figure 5.6. Overview of the Gridding and Partitioning (GaP) procedure as applied to monomers, exemplified using phenylalanine as a potential primary amine. This molecule thus contains two pharmacophoric groups (the aromatic ring and the carboxylic acid). During the conformational analysis the locations of these pharmacophoric groups are tracked within a regular grid. See color insert. [Reproduced from A. R. Leach and M. M. Hann, Drug Discovery Today, 5, 326-336 (2000),...

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