%0 Journal Article
%T DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening
%A David Lagorce
%A Tania Pencheva
%A Bruno O Villoutreix
%A Maria A Miteva
%J BMC Chemical Biology
%D 2009
%I BioMed Central
%R 10.1186/1472-6769-9-6
%X Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine.DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes to explore molecular mechanisms is very complex, time consuming and costly. In recent years, various in silico approaches have been reported and are now commonly used prior to or to complement experimental screening techniques with the aim of facilitating the overall process. In particular, virtual screening (VS) methods such as structure-based (SBVS) and/or ligand-based (LBVS) allow to screen thousands or millions of small molecules against a biomolecular target [1,2], and therefore, these approaches play an increasingly important role in modern drug discovery programs. SBVS makes use of docking and scoring techniques to orient and rank small molecules in the context of the protein-binding site, searching for shape and chemical complementarities [3-5]. The general concept behind ligand-based
%U http://www.biomedcentral.com/1472-6769/9/6