TY  - JOUR
A1  - Hähnke, Volker Dirk
A1  - Hofmann, Bettina Petra
A1  - Proschak, Ewgenij
A1  - Steinhilber, Dieter
A1  - Schneider, Gisbert
T1  - PhAST : pharmacophore alignment search tool
T2  - Chemistry central journal
N2  - 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. 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. 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, MOE pharmacophore quadruples) in retrospective virtual screenings using the COBRA 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.
KW  - Virtual Screening
KW  - Lead Structure
KW  - Identical Topology
KW  - Compound Database
KW  - Pairwise Sequence Alignment
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6786
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-66695
SN  - 1752-153X
N1  - © 2009 Hähnke et al; licensee BioMed Central Ltd.
VL  - 3
IS  - (Suppl 1):P67
SP  - 1
EP  - 1
PB  - BioMed Central
CY  - London
ER  -