Working with MED-Ligand
Working with the computational fragment based drug design protocol is a combination of a target based drug design approach, MED-SuMo, followed by an advanced 2D and 3D cheminformatics with MED-Ligand:
MED-SuMo makes it possible to populate in 3D any protein surface of interest with MED-Portion chemical moieties
MED-Ligand combines 3D MED-Portion chemical moieties from MED-SuMo into potential ligands
MED-Ligand can do much more than hybridising: filter and classify hybrids
By taking advantage of the PDB exponential growth, MED-Ligand is actually able to generate a large number of innovative compounds in most of the cases. Because MED-Portion chemical moities and all output molecules originate from the selected chemical libraries, it produces material that adheres to the medicinal chemistry area. Compared to other de novo methods in fragment based drug design, MED-Ligand is the first protocol to take advantage of both chemical information from the PDB and chemical suppliers lists to deliver new active compounds to medicinal chemists.
Applying the computational fragment based drug design protocol with MED-SuMo and MED-Hybridise
Define the protein surface where you want to design ligands in 3D: sites or full surface
Compare this surface with MED-SuMo to a new proprietary database encoding MED-Portions, a complete set of protein-fragment interactions extracted by crossing the PDB and any chemical databases. MED-SuMo will retreive any hit that has similar 3D interactions (chemical features and shape).
Browse those MED-Portions chemical moieties fitting into your binding query into the MED-SuMo graphical interface: optionally filter out low score hits or unwanted clusters.
Hybridise in 3D those MED-Portion chemical moieties with methods implemented into the MED-LigandGraphical User interface ; optionally remove duplicate on 2D or 3D rules and control the level of diversity.
Browse at each step molecules matching any chemical database supplier.
Interfaces
MED-Ligand is a user friendly software available as a Graphical User Interface and a Command Line Interface
Running Windows: 2000, server 2003, XP and Vista and Linux systems,
CLI is integrated with Scitegic Pipeline Pilot,
CLI takes advantage of state of the art hardware architectures: multicore processors and computer clusters.
References
[1] Moriaud F, Henry T., Adcock S.A., Vorotynsev A.M., Martin L., Doppelt O., De Brevern A.G., Delfaud F. “Lead optimization computational protocol at PDB scale to rationally optimize attachments to a given kinase inhibitor scaffold”, Virtual Discovey, 2008 23-24 january, Palm Springs, CA, USA (Poster)
[2] Moriaud F., Henry T., Adcock S.A., Vorotynsev A.M., Martin L., Doppelt O., De Brevern A.G., Delfaud F "A computational protocol to fragment-based drug design at PDB scale" Chemistry Central Journal 2008, 2(Suppl 1):S6 from 3rd German Conference on Chemoinformatics Goslar, Germany. 11-13 November 2007
[3] Moriaud F., Adcock S.A., Vorotyntsev A.M., Martin L., Doppelt O., De Brevern A.G. and Delfaud F. “A computational protocol to Fragment-Based Drug Design at PDB scale”, eCheminfo InterAction Meeting, Bryn Mawr, 2007 October 15-19, Philadelphia, PA, USA (Talk)
[4] Moriaud F., Adcock S.A., Vorotyntsev A.M., Martin L., Doppelt O., De Brevern A.G. and Delfaud F. “A computational protocol to Fragment-Based Drug Design at PDB scale”, ACS Fall 2007 prospectives Advances in Structure Based Drug Discovery, 2007 September 9-11, San Francisco, CA, USA (Poster)
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