Recent advances in high-throughput protein structure determination and in computational chemistry have refocused attention on virtual screening and fast automated docking methods. This review provides a brief introduction to the basic ideas and outlines computational tools currently used. We also provide several examples of where virtual screening has proved successful, highlighting the usefuln...

Dualor multi-target ligands have gained increased attention in the past years due to several advantages, including more simple pharmacokinetic and phamarcodynamic properties compared to a combined application of several drugs. Furthermore multi-target ligands often possess improved efficacy [1]. We present a new approach for the discovery of dual-target ligands using aligned pharmacophore model...

Electrostatic forces play a large role in determining the strength of protein-ligand interactions, and the calculation of pKa value shifts upon ligand binding is therefore an important component of any accurate protein-ligand binding calculation. However, such pKa calculations are rarely performed in virtual screening experiments due to the unavailability of ligand solution pKa values and the d...

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybri...

We wanted to discover novel chemotypes for 2 targets which lacked x-ray data, CCK2 and 11beta-HSD1. Our approach was to undertake ligand-based virtual screening using the molecular fields of active compounds as our template to define activity. Our hypothesis was that the field pattern of an active molecule describes its key binding features and molecules with a similar field have a high probabi...

Large scale grids for in silico drug discovery open opportunities of particular interest to neglected and emerging diseases. In 2005 and 2006, we have been able to deploy large scale virtual docking within the framework of the WISDOM initiative against malaria and avian influenza requiring about 100 years of CPU on the EGEE, Auvergrid and TWGrid infrastructures. These achievements demonstrated ...

Three dimensional pharmacophores and pharmacophore searches are well established in virtual screening and have been applied successfully in many prospective and retrospective drug discovery campaigns [1]. While the pharmacophore concept offers an easy and abstract understanding of molecular properties, plenty of user intervention is required to define feasible models. Recently, Silicos NV provi...