Advanced Cheminformatics

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In addition to standard cheminformatics methods and tools, we have developed robust hit enrichment methodologies, based on field fingerprints and multidimensional pharmacaphores. The field fingerprint is an evolution of a chemical fingerprint. The normalized informational content of a field fingerprint is what makes it superior to the conventional hash-based chemical fingerprint.

 Figure 4.

Consider the example of application of the fingerprints in a hit-to-lead optimization scenario (Figure 4).  The structure of an initial HTS hit was used to compute fingerprint distances against multiple in vitro validated derivatives of this hit. The computed distances were then successfully correlated with the experimentally obtained IC50 values of the hit derivatives. The Q-MOL field fingerprints are ideal for chemical scrambling of already patented drugs.

The multidimensional 3D pharmacophores is another cheminformatics innovation aimed to simplify hit-to-lead ligand optimization under conditions of insufficient or abscent receptor structural data. Given a set of validated ligands, an array of three-dimensional maps can be constructed based on physico-chemical similarities derived from ligand structures. These maps form the field potential of a set of ligands (Figure 5).
Figure 5.