Interaction fingerprints

Deng et al. [18] recently described an approach to representing and analyzing 3D protein-ligand binding interactions. The Structural Interaction Fingerprint (SIFt see also Chapter 10) method represents a ligand by the interactions it un-... 

Deng, Z., Chuaqui, C., Singh, J., Structural interaction fingerprint (SI Ft) A novel method for analyzing three-dimensional protein-ligand binding interactions. J. Med. Chem. 2004, 47, 337-344. 

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

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. 

A structural interaction fingerprint is a ID binary representation of the interaction patterns from a 3D protein-inhibitor complex. The fingerprint representation of the interaction patterns is compact and allows for rapid clustering and analysis of massive numbers of complexes. 

We have developed a profile-based approach termed p-SIFt [7] that enables us to describe the conservation of interactions between a set of protein-ligand receptor complexes. The use of profiles provides a sensitive means to compare and contrast multiple inhibitors binding to a drug target. A structural interaction fingerprint profile (p-SIFt) represents the degree to which interactions are conserved across a set of ligand-receptor complexes. The p-SIFt, P(r), is derived from an array, denoted below as b, of SIFt patterns and its derivation from a set of SIFts is shown in Fig. 10.2. 

Because the interaction fingerprint represents the binding mode of a ligand to a target protein, similar fingerprints imply that the corresponding ligands make similar interactions with the protein. 

Clustering of Kinase Inhibitors Based on Interaction Fingerprints... 

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... 

Knowledge based identification of potent antitubercular compounds using structure based virtual screening and structure interaction fingerprints. J Chem Inf Model 49 35 2... 

Z. Deng, C. Chuaqui, J. Singh, Structural Interaction Fingerprint (SIFt) A... 

Mpamhanga, C.P., Chen, B McLay, I.M. and Willett, P. (2006) Knowledge-based interaction fingerprint scoring a simple method for improving the effectiveness offast scoring functions./. Chem. Inf. Model, 46, 686-698. 

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... 

Venhorst J, Nunez S, Terpstra JW et al (2008) Assessment of scaffold hopping efficiency by use of molecular interaction fingerprints. J Med Chem 51 3222-3229... 

Structural interaction fingerprint (SIFt) a novel method for analyzing three-dimensional protein—ligand binding interactions. Joumol of Medicinal Chemistry, 47, 337—344. 

Topological Scoring by Protein-Ligand Interaction Fingerprint (IFP)... 

Brewerton, S.C. (2008) The use of protein-ligand interaction fingerprints in docking. Current Opinion in Drug Discovery Development, 11, 356-364. 

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