Side effects can be predicted and/or clarified at biomolecular level. Compounds most likely to succeed can be selected for the subsequent phases of the Drug Discovery process (Reduction of the Attrition Rate) Therapies with the best response and the highest safety margin to ensure patient care can be tailored (Personalized medicine)
Identifying drugs to be re-used for new indications saves having to retrace the long and expensive process of clinical trials.
Selecting drug candidates able to interfere with multiple nodes (proteins) belonging to the same pathological network improves the effectiveness of the therapeutic compounds.
SPILLOproject is aimed at developing and using new computational technologies for the drug discovery, providing in silico services for public and private research centers. A central role is played by the innovative software SPILLO-Potential Binding Sites Searcher (SPILLO-PBSS)
SPILLO-PBSS is an innovative computational tool that can be integrated into the standard rational drug discovery paradigm to reduce the attrition rate typical of the Drug Discovery and Development (DD&D) process. The possibility to predict potential binding sites of a small molecule (e.g. a hit or a lead compound, a drug candidate, a drug) within an arbitrary protein 3D-structure represents a desired goal to speed up various phases of the DD&D process, including side-effects prediction/clarification (de-risking strategy). SPILLO-PBSS is based on a new physicochemical approach which allows to carry out the virtual screening of the whole available human structural proteome (15000+ protein 3D-structures) with relatively limited computational resources. SPILLO-PBSS is able to predict the potential off-target proteins of a small molecule, as well as the locations of the potential binding-sites on each single protein and the relative orientation of the small molecule.
The uniqueness of SPILLO-PBSS lies in its ability to find the potential binding sites even if they are highly distorted and/or apparently inaccessible (e.g: closed, buried, occupied) to the small molecule with respect to an ideal conformation suitable for the binding. In comparison to the other existing tools, SPILLO-PBSS is more likely to find proteins responsible for side-effects and/or for additional positive effects of the small molecule (Polypharmacology, Drug repositioning).