PhAST : pharmacophore alignment search tool

We developed the Pharmacophore Alignment Search Tool (PhAST), a text-based technique for rapid hit and lead structure searching in large compound databases. For each molecule, a two-dimensional graph of potential pharmac
We developed the Pharmacophore Alignment Search Tool (PhAST), a text-based technique for rapid hit and lead structure searching in large compound databases. For each molecule, a two-dimensional graph of potential pharmacophoric points (PPPs) is created, which has an identical topology as the original molecule with implicit hydrogen atoms. Each vertex is coloured by a symbol representing the corresponding PPP. The vertices of the graph are canonically labelled [1]. The symbols associated with the vertices are combined to a so-called PhAST-Sequence beginning with the vertex with the lowest canonical label. Due to the canonical labelling the created PhAST-Sequence is characteristic for each molecule. For similarity assessment, PhAST-Sequences are compared using the sequence identity in their global pairwise alignment [2]. The alignment score lies between 0 (no similarity) and 1 (identical PhAST-Sequences). In order to use global pairwise sequence alignment, a score matrix for pharmacophoric symbols was developed and gap penalties were optimized. PhAST performed comparably and sometimes superior to other similarity search tools (CATS2D [3], MOE pharmacophore quadruples [4]) in retrospective virtual screenings using the COBRA [5] collection of drugs and lead structures. Most importantly, the PhAST alignment technique allows for the computation of significance estimates that help prioritize a virtual hit list.
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Metadaten
Author:Volker Hähnke, Bettina Petra Hofmann, Ewgenij Proschak, Dieter Steinhilber, Gisbert Schneider
URN:urn:nbn:de:hebis:30-66695
Document Type:Article
Language:English
Date of Publication (online):2009/08/26
Year of first Publication:2009
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2009/08/26
Note:
© 2009 Hähnke et al; licensee BioMed Central Ltd.
Source:4th German Conference on Chemoinformatics Goslar, Germany. 9–11 November 2008 ; Chemistry Central Journal 2009, 3(Suppl 1):P67 ; doi:10.1186/1752-153X-3-S1-P67 ; http://www.journal.chemistrycentral.com/content/3/S1/P67
HeBIS PPN:215153618
Institutes:Biochemie und Chemie
Dewey Decimal Classification:540 Chemie und zugeordnete Wissenschaften
Sammlungen:Universitätspublikationen
Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

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