V-SYNTHES powered by MolSoft ICM-VLS

With V-SYNTHES you can screen the 21 Billion Enamine REAL Space efficiently and accurately.

MolSoft's ICM accurate flexible docking, cheminformatics and virtual screening technology provided the unique and powerful engine for a successful screen of as many as 11 billion chemical compounds, potential drug candidates. The USC laboratory of Prof. Vsevolod Katritch report in Nature an approach called V-SYNTHES. The tool performs a ICM-docking based hierarchical structure-based screening of a Enamine REAL Space giga library. The screen resulted in the discovery of new lead compounds for the GPCR CB2 and the Kinase ROCK1.

For many years, MolSoft has been developing methods for fast accurate docking and scoring tools, and incorporating those tools to search giga-sized libraries. These tools include, ICM-Pro docking, GIGA search, and a shape property-based pharmacophoric search method called RIDE. GIGA search and RIDE were applied to the NIH SAVI database and Enamine REAL database.

For V-SYNTHES, ICM-Pro was used as the docking engine as well as for the preparation of the reaction libraries and enumeration of the giga-sized virtual databases. Docking and screening simulations were then undertaken using MolSoft's ICM-Pro Virtual Ligand Screening tools. The docking uses MolSoft's Biased Probability Monte Carlo method, optimized force field, docking score to dock and score fragments of a combinatorial library, and then an empirical score is derived and applied to a much larger library. At the end, the top scoring hits from the library are re-docked and scored again. This hierarchical protocol accelerates the docking and scoring run and makes it applicable to very large databases. The flexibility of the binding pocket was represented using MolSoft's 4D docking methodology which uses an ensemble of structures efficiently for fast and accurate flexible-receptor ligand docking. Prof. Katritch at USC says "We are very excited to use the MolSoft ICM-Pro technology to address the challenges of screening very large chemical databases for the discovery of drug candidates."

You can view and download additional ICM scripts used for this work at the Katritch lab GitHub site which are ready for use with the ICM-Pro + VLS desktop modeling software.

Please contact MolSoft (www.molsoft.com info@molsoft.com) if you have any questions about how to apply this approach to your drug discovery program.