Structural 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. 

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. 

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... 

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

The need for an overall and combined chemical structure and data search system became clear to us some time ago, and resulted in the decision to build CHIRBASE, a molecular-oriented factual database. The concept utilized in this database approach is related to the importance of molecular interactions in chiral recognition mechanisms. Solely a chemical information system permits the recognition of the molecular key fingerprints given by the new compound among thousands of fingerprints of known compounds available in a database. 

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