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Predicting molecular interactions is a major goal in rational drug
design. Pharmacophore, which is the spatial arrangement of features that is
essential for a molecule to interact with a specific target receptor, is
important for achieving this goal.
PharmaGist is a freely available web server for pharmacophore
detection. The employed method is ligand based. It does not require
the structure of the target receptor. Instead, the input is a set of
structures of drug-like molecules that are known to bind to the
receptor. We compute candidate pharmacophores by multiple flexible
alignments of the input ligands. The main innovation of this approach
is that the flexibility of the input ligands is handled explicitly and
in deterministic manner within the alignment process. The method is
highly efficient, where a typical run with up to 32 drug-like
molecules takes seconds to a few minutes on a stardard PC. Another
important characteristic of the method is the capability of detecting
pharmacophores shared by different subsets of input molecules. This
capability is a key advantage when the ligands belong to different
binding modes or when the input contains outliers.
The download version includes virtual screening capability. The performance of PharmaGist for virtual screening was successfully evaluated on a commonly used data set of G-Protein Coupled Receptor alpha1A. Additionally, a large-scale evaluation using the DUD (directory of useful decoys) data set was performed. DUD contains 2950 active ligands for 40 different receptors, with 36 decoy compounds for each active ligand. PharmaGist enrichment rates are comparable with other state-of-the-art tools for virtual screening.
If you use this webserver, please cite:
1. Inbar Y, Schneidman-Duhovny D, Dror O, Nussinov R, Wolfson HJ. Deterministic Pharmacophore Detection via Multiple Flexible Alignment of Drug-Like Molecules. In Proc. of RECOMB 2007, vol. 3692 of Lecture Notes in Computer Science, pp. 423-434. Springer Verlag.
2. Schneidman-Duhovny D, Dror O, Inbar Y, Nussinov R, Wolfson HJ. PharmaGist: a webserver for ligand-based pharmacophore detection. Nucleic Acids Research 2008. [Abstract ] [FREE Full Text ]
3. Dror O, Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. Novel approach for efficient pharmacophore-based virtual screening: method and applications. J Chem Inf Model. 2009 Oct;49(10):2333-43. [Abstract ] [Full Text ]