Fingerprints docking

One or more lead molecules may be used as a focusing target. Similarity metrics include Daylight fingerprint Tanimoto similarity. The penalty score for each compound in the library is defined as the distance between it and the most similar lead molecule. The penalty score for the library is the average of the individual compound penalty scores. QSAR predictions and docking scores can also be used in this term. 

Decornez et al. used a generalized kinase model and a combination of 2D (fingerprint based similarity) and 3D methods (docking) to develop a kinase family focused library (15). The authors used 2800 kinase inhibitors compounds as a reference for a 2D search of their in-house database of 260 compounds... 

Kelly, M.D., Mancera R.L., Expanded interaction fingerprint method for anlays-ing ligand binding modes in docking and structure-based dmg design. J. 

UNITY pharmacophore, FlexXd docking, and structure interaction fingerprint approaches were used to identify compounds in the Maybridge database (59,275 compounds) as potential thymidine monophosphate kinase inhibitors... 

Briem H, Kuntz ID, Molecular similarity based on dock-generated fingerprints, J. Med. Chem., 39 3401-3408, 1996. 

ELAP can be used for automatic generation of site points for docking, automatic generation of 3D fingerprints descriptors for ligands and proteins ready for che-mometric analyses and lead optimization. After a brief review of the theory underpinning the ELAP software, this chapter will illustrate some of its applications and case studies. 

Figure 5.8. Example of privileged four-point pharmaeophores, either ereated from a ligand using a particular feature (e.g., the centroid of a "privileged" substructure) or complementary to a protein site using a site point or attachment point of a docked scaffold. Only pharmacophores that include this special feature are included in the fingerprint, thus providing a relative measure of diversity 1 similarity with respect to the privileged feature.

Briem, H. and Kuntz, I.D. (1996). Molecular Similarity Based on DOCK-Generated Fingerprints. J.Med.Chem., 39,3401-3408. 

Fig. 2 Converting a reference protein-ligand complex (REF, bottom left) into an interaction fingerprint (IFP) registering seven possible interactions with binding site residues. Docked poses (bottom right) are fingerprinted and the corresponding IFPs compared to the reference IFP using a standard Tanimoto coefficient. The best pose (pose 6, bottom center) exhibits the highest IFP similarity to the reference...

Marcou G, Rognan D (2007) Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. J Chem Inf Model 47 195-207... 

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