Screening of virtual library

In view of latter developments (see Sections 16.4.9-16.4.11 for further details) the procedure, even with simplifications such as using a single CONCORD/ CORINA-derived 3D geometry instead of performing a Monte Carlo conformational search, is too computationally expensive to be applied to e-screening of virtual libraries. However, it may still be a useful alternative/complement for computing more detailed information about a compound, or to provide a more easily interpretable model to complement other models based on more rapidly computable parameters but which are difficult to interpret in terms of how to modify compounds in order for them to have better intestinal absorption characteristics. 

An approach we term Virtual Screening of Virtual Libraries (VSVL) is intended to take advantage of our in-house automated synthesis capabilities. This involves the creation of large 3-D databases of virtual libraries using the Catalyst system [20]. Catalyst uses a prestored set of conformations for each molecule, so while construction of the... 

Green, D. V. (2003) Virtual screening of virtual libraries. Prog Med Chem 41, 61-97. 

Virtual screening of virtual libraries, or virtual library construction, enables hitherto unknown parts of chemical space to be explored. 

Tanimoto index > 0.9 but may be very different in terms of activity (chemically similar, biologically diverse), while completely different strucmres are known to have the same biological activity (chemically diverse, biologically similar). This intrinsic drawback to the computational screening of virtual libraries should always be considered when interpreting screening results of a computationally designed library, and real data should be used to refine any virtual SAR information based on chemical similarity or dissimilarity. 

In view of these studies Balakin et al. [22] concluded that there is no statistical support for the idea that 3D descriptors are more appropriate for prediction of aqueous solubility of chemicals compared to 2D or ID methods. Because of the difficulties in generating and finding conformational minimum for 3D structures, one should initially try more simple indexes based on molecular topology. The big advantage of the later method is their speed 2D methods can typically process tens of thousands of molecules per second, and that makes them very useful for screening of virtual libraries of compounds. 

The objective of the present work was screening of virtual library of functional monomers with the aim to identify the monomers capable of interacting with ephedrine (Fig. 11). 

Shoichet BK. Virtual screening of chemical libraries. Nature 2004 432 862-5. 

The next vague of tools will be around computational or in silico ADME approaches. These will allow to include ADME into the design of combinatorial libraries, the evaluation of virtual libraries, as well as in selecting the most promising compounds to go through a battery of in vitro screens, possibly even replacing some of these experimental screens. Several of these computational tools are currently under development as will be discussed in this volume. 

Finally, the 3D-LogP descriptor may be used for the 3D screening of virtual molecular conformation libraries wherein the selection of candidate molecules might not only be driven by pharmacophoric but also by physicochemical constraints. Similarly, we anticipate that the 3D-LogP descriptor will also become useful for the design of chemical libraries in which the description of the conformational space is taken into account in the description of the constituent molecules. We are currently enhancing the descriptor by implementing the last atom type classification system proposed by Wildman and Crippen (54). 

D., Wang, . C. (2001) Virtual screening of combinatorial libraries across a gene family in search of inhibitors of Giardia lamblia guanine phosphoribosyltransferase. Antimi-crob Agents Chemother 45, 2571-2576. 

Ghosh, S., Nie, A., An, J., Huang, Z. (2006) Structure-based virtual screening of chemical libraries for drug discovery. Curr Opin Chem Biol 10, 194-202. 

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