The study reports a flexible structure-based approach aimed at identifying binding sites within target proteins starting from a well-defined reference binding site. The method, named SPILLO potential binding sites searcher (SPILLO-PBSS), includes a suitably designed tolerance which allows an efficient recognition of the potential binding sites regardless of both involved residues and protein conformation. Hence, the proposed method overcomes the rigidity which affects the available approaches and which prevents a proper analysis of distorted binding sites. We apply SPILLO-PBSS to several test cases, including the search for the guanosine diphosphate binding site in distorted H-Ras proteins and the identification of acetylcholine binding proteins from among a library of heterogeneous resolved proteins. Tests are also performed to compare SPILLO-PBSS with other related and available methods. The encouraging results confirm the notable potentialities of this approach and lay the foundation for its use to analyze and predict target proteins on a proteome-wide scale.

SPILLO-PBSS : detecting hidden binding sites within protein 3D-structures through a flexible structure-based approach / A. Di Domizio, A. Vitriolo, G. Vistoli, A. Pedretti. - In: JOURNAL OF COMPUTATIONAL CHEMISTRY. - ISSN 0192-8651. - 35:27(2014), pp. 2005-2017. [10.1002/jcc.23714]

SPILLO-PBSS : detecting hidden binding sites within protein 3D-structures through a flexible structure-based approach

A. Vitriolo;G. Vistoli
Penultimo
;
A. Pedretti
Ultimo
2014

Abstract

The study reports a flexible structure-based approach aimed at identifying binding sites within target proteins starting from a well-defined reference binding site. The method, named SPILLO potential binding sites searcher (SPILLO-PBSS), includes a suitably designed tolerance which allows an efficient recognition of the potential binding sites regardless of both involved residues and protein conformation. Hence, the proposed method overcomes the rigidity which affects the available approaches and which prevents a proper analysis of distorted binding sites. We apply SPILLO-PBSS to several test cases, including the search for the guanosine diphosphate binding site in distorted H-Ras proteins and the identification of acetylcholine binding proteins from among a library of heterogeneous resolved proteins. Tests are also performed to compare SPILLO-PBSS with other related and available methods. The encouraging results confirm the notable potentialities of this approach and lay the foundation for its use to analyze and predict target proteins on a proteome-wide scale.
Binding site detection; Drug repositioning; Molecular recognition; Off-target proteins; Protein druggability; Acetylcholine; Algorithms; Binding Sites; Guanosine Diphosphate; Models, Molecular; Protein Conformation; Proteins; Proteome; Computational Biology; Software; Computational Mathematics; Chemistry (all)
Settore CHIM/08 - Chimica Farmaceutica
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/340692
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 8
social impact