Virtual screening three-dimensional

Several research groups have built models using theoretical desaiptors calculated only from the molecular structure. This approach has been proven to be particularly successful for the prediction of solubility without the need for descriptors of experimental data. Thus, it is also suitable for virtual data screening and library design. The descriptors include 2D (two-dimensional, or topological) descriptors, and 3D (three-dimensional, or geometric) descriptors, as well as electronic descriptors. 

In this chapter, we describe a simple and robust approach for representing and analyzing three-dimensional protein-ligand complexes called SIFt (Structural Interaction Fingerprint) [6, 7]. We will show how this method can be applied to organizing and analyzing the structural information within the protein kinase family and also how this can be applied to virtual screening for inhibitors. 

Phannacopbore The ensemble of sicric. electronic, and lipophilic factors needed to ensure interaction of a drag molecule with a given receptor. Pharmacophores are most useful in searching a three-dimensional (3D) structure dalaba.se and in filtering structures for virtual screening. 

The new set of varied DF found in the previous section can be studied in the same way as the well-known eDF maps are represented since the first plots used in Quantum Chemistry [53a)]. Here an alternative point of view, similar as the one used by Mezey [9a)], will be chosen. Three-dimensional maps of isodensity surfaces can be generated with available computational techniques [84]. This corresponds to follow several steps, some of them so trivial that appear to be irrelevant in a study as the present. The representation process starts with the evaluation of DF grids, enveloping the molecular co-ordinates, which can origin wireframe structures related with the isodensity values. After that, they can be rendered and rotated in space as virtual objects, until some adequate point of view is found. Finally, the chosen object snapshot can be manipulated, represented on a screen and, if necessary, printed into a paper surface. The processing detail, the computational techniques and the required programs and data are briefly commented in Appendix E. All the necessary items are available to the interested reader and permit to generate surfaces of his own [93-96]. 

Wabunde, T., Giegerich, C., and Evers, A. (2009) Sequence-derived three-dimensional pharmacophore models for G-protein-coupled receptors and their application in virtual screening. Journal of Medicinal Chemistry, 52, 2923-2932. 

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