Fingerprints for ligands and proteins

Baroni M, Cruciani G, Sciabola S et al (2007) A common reference framework for analyz-ing/comparrng proteins and ligands. Fingerprints for ligands and proteins (FLAP) theory and application. J Chem Inf Model 47 279-294... 

FLAP fingerprints (FLAP stands for Fingerprints for Ligands and Proteins) are vectorial descriptors encoding information about 3- and 4-point pharmacophores [Perruccio, Mason etal, 2006 Baroni, Crucianiet al, 2007]. The theory underpinning FLAP is similar to that of the TOPP descriptors. 

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. 

Atoms in molecules are first classified into different pharmacophoric types by the GRID force field parametrization. Features considered are hydrophobicity, hydrogen-bond donor and acceptor capabilities, and charge. Then, all accessible geometries for all the combinations of three or four features are calculated and encoded in the final vector. Fingerprints can be calculated both for ligands and proteins. In small ligands, pharmacophores are defined by triplets or quartets of atoms, vhich have critical interactions with a receptor. 

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. 

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