A short description of SPILLO-PBSS
SPILLO-Potential Binding Sites Searcher (SPILLO-PBSS) is an innovative software purposely designed to identify target and off-target proteins of a small molecule (e.g., a drug) within very large protein structural databases (e.g., the whole available human structural proteome). It relies on the accepted hypothesis that protein binding site similarity of target proteins plays a key role in drug promiscuity.
SPILLO-PBSS is able to identify off-target proteins with no sequence nor structural homology to the main target of the small-molecule, even if the potential binding sites are strongly distorted (e.g., completely closed, buried, occupied) compared to a conformation suitable for the binding.
Such a unique feature allows SPILLO-PBSS to overcome the main drawback of the traditional existing approaches, which are liable to miss off-target proteins responsible for drug adverse effects, whenever their binding sites are not already in a suitable conformation for the binding event (see Table 2 of the reference paper for a comparison with other related available methods).
All proteins included in a database are analyzed, searching for potential binding sites (PBSs) similar to a binding site used as reference, the RBS, obtained either from experiments or from modelling. A list of the potential target and off-target proteins of the drug is then provided by the software, ranked according to a score representing the similarity between their PBS and the RBS.
Many structural details concerning both the amino acid residues included in the PBSs and their interactions with the drug are also provided by SPILLO-PBSS.
- Fast identification of target and off-target proteins of a drug on a proteome-wide scale
- Identification of target and off-target proteins with no sequence nor structural homology to the main target of the drug
- Innnovative flexible structure-based approach
- Prediction and clarification of drug adverse off-target effects at a biomolecular level
- Identification of targets involved in polypharmacological effects of a drug
- Identification of targets useful for new indications of a drug (Drug repositioning)
- Reduction/optimization of animal testing
- Ability of identifying drug binding sites even if strongly distorted or completely closed
- Totally unbiased search for drug binding sites in protein structures, including both surface and inner regions
Advantages over other existing tools
- Higher probability of success (POS) in drug targets and off-targets identification on a proteome-wide scale
- Superior ability in identifying potential drug binding sites even if strongly distorted compared to a suitable conformation for the binding
 A. Di Domizio et al., SPILLO-PBSS: Detecting Hidden Binding Sites within Protein 3D-Structures Through a Flexible Structure-Based Approach. J. Comput. Chem. (2014); DOI: 10.1002/jcc.23714
 V. Joachim Haupt et al., Drug Promiscuity in PDB: Protein Binding Site Similarity Is Key. PLOS One (2013); DOI: 10.1371/journal.pone.0065894
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