Introduction to Virtual Screening

    Screen is a software suite that provides tools for pharmacophore analysis, screening and selectivity optimizations.

    Biologically active compounds usually bind to their specific receptors by weak forces. These molecular interactions include hydrogen binding, electrostatic attraction, hydrophobic affinity etc. The existence of so-called pharmacophore pointsin the appropriate positions is often required for receptor binding. The pharmacophore pattern of a molecule can be determined with the help of the PMapper tool.

    The comparison of molecular structures is based on the comparison of calculated molecular descriptors. The analysis of structural, chemical and pharmacophoreproperties using fingerprints helps recognizing molecules with similar biological activities. ScreenMD is equipped with various mathematical methodsfor the dissimilarity screening of molecules.

    When we know that a set of biologically active compounds acts on the same receptor, the "common part" can be identified as a hypothesis. Since all active compounds contain the hypothesis, it can be presumed that its existence is essential for the biological activity. The ScreenMD utility can select molecules from huge molecule databases similar to biologically active compounds such as drugs. Sometimes the structure of the found molecules is not chemically similar to known active compounds, but they are similar to the pharmacophore hypothesis.

    The pharmacophore mapping and screening tools are highly customizable. Although there is no "best" screening methodology or screening parameter set in general, the screening selectivity can be increased dramatically for a given molecule family by fine tuning the screening parameters. ChemAxon developed a screening package that helps to find the best parameter set (descriptors, metrics, normalization, weighting, scaling, directing) for each compound family. The enrichment ratioof the screening procedure can be higher even by an order of magnitude using an optimized parameter set compared to unoptimized standard screening methodologies.