Discovery and Lead Optimisation System: an integrated
system of programs for virtual molecular libraries
and rational drug design
Funding programme: D.M. 593/2000 art. 11, Fondo Agevolazioni Ricerca MIUR
Start – end year: 2004 – 2007
For this project Consorzio Milano Ricerche acting as subcontractor of Delos
In the recent ten years, the increased number of molecular targets is leading to a change in pharmaceutical research: in spite of increasing R&D investments, the number of new drugs is declining. A possible solution is given by Virtual High Throughput Screening (VHTS), a technique with the peculiarity to go hand in hand with conventional experimental procedures. Moreover the efficiency scales-up linearly with the number of processors.
Hence, DELOS is proposing a bioinformatic integrated platform (hardware and software) covering the whole Rational Drug Design paradigm (RDD). The complete analysis of a virtual library of 105 compounds, with the extraction of a subset library of approximately 200 lead-compounds can take on a parallel architecture composed of 20 processors 10 days.
The RDD framework integrated in DELOS is composed of four phases:
- Determination and refinement of the 3D structure of a target protein.
- Virtual molecular library generation by means of computational combinatorial chemistry elements).
- Docking simulations between a subset of molecules of the library and the receptor.
- Machine learning approaches for the development of a statistical model for correlation and prediction of biological activity.