A short description of SPILLO-PBSS

SPILLO-Potential Binding Sites Searcher (SPILLO-PBSS)^[1] is an innovative software purposely designed to identify target and off-target proteins of any small molecule (e.g., a drug) within very large protein structural databases (e.g., the whole available human structural proteome). 

SPILLO-PBSS is able to identify targets and off-targets with no sequence nor structural homology to the main target of the small-molecule, even when 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 traditional approaches, which are liable to miss, for example, off-target proteins responsible for adverse effects of a drug, whenever their binding sites are not already in a suitable conformation for the binding event (see Table 2 of the reference paper^[1] for a comparison with other related available methods).

A list of the potential target and off-target proteins of the drug is then provided by the software, along with many structural details concerning their potential binding sites.

Concept

- 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

Uses

- Prediction and clarification of drug adverse off-target effects at 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 (according to the 3Rs principle)

Uniqueness

- 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

Experimental validations [LINK]

REFERENCES:

[1] 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