title: Pharao: pharmacophore alignment and optimization.
abstract: Within the context of early drug discovery, a new pharmacophore-based tool to score and align small molecules (Pharao) is described. The tool is built on the idea to model pharmacophoric features by Gaussian 3D volumes instead of the more common point or sphere representations. The smooth nature of these continuous functions has a beneficent effect on the optimization problem introduced during alignment. The usefulness of Pharao is illustrated by means of three examples: a virtual screening of trypsin-binding ligands, a virtual screening of phosphodiesterase 5-binding ligands, and an investigation of the biological relevance of an unsupervised clustering of small ligands based on Pharao.
authors.affiliation: Silicos NV, Wetenschapspark 7, B-3590 Diepenbeek, Belgium. hans.dewinter@silicos.com
authors.forename: Jonatan
authors.initials: J
authors.lastname: Taminau
authors.forename: Gert
authors.initials: G
authors.lastname: Thijs
authors.forename: Hans
authors.initials: H
authors.lastname: De Winter
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D016503:Drug Delivery Systems; D015195:Drug Design; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands