In this work, the information contained in the contacts between fragments of small-molecule ligands and protein residues has been collected and its exploitability has been verified by using the scoring of docking simulations as a test case for bringing about a proof of concept. Contact statistics between small-molecule fragments and binding site residues were collected and analyzed using a dataset composed of 200,000+ binding sites and associated ligands, derived from the database of the LIBRA ligand binding site recognition software, as a starting point. The fragments were generated by applying the decomposition algorithm implemented in BRICS. A simple “potential” based on the contact frequencies was tested against the CASF-2013 benchmark; its performance was then evaluated through the rescoring of docking poses generated for the DUD-E dataset. The results obtained indicate that this approach, its simplicity notwithstanding, yields promising results that are comparable, and in some cases, superior, to those obtained with other, more complex scoring functions.

Macari, G., Toti, D., Del Moro, C., Polticelli, F., Fragment-based ligand-protein contact statistics: Application to docking simulations, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2019; 20 (10): 2499-2516. [doi:10.3390/ijms20102499] [http://hdl.handle.net/10807/163223]

Fragment-based ligand-protein contact statistics: Application to docking simulations

Toti, D.
Secondo
;
2019

Abstract

In this work, the information contained in the contacts between fragments of small-molecule ligands and protein residues has been collected and its exploitability has been verified by using the scoring of docking simulations as a test case for bringing about a proof of concept. Contact statistics between small-molecule fragments and binding site residues were collected and analyzed using a dataset composed of 200,000+ binding sites and associated ligands, derived from the database of the LIBRA ligand binding site recognition software, as a starting point. The fragments were generated by applying the decomposition algorithm implemented in BRICS. A simple “potential” based on the contact frequencies was tested against the CASF-2013 benchmark; its performance was then evaluated through the rescoring of docking poses generated for the DUD-E dataset. The results obtained indicate that this approach, its simplicity notwithstanding, yields promising results that are comparable, and in some cases, superior, to those obtained with other, more complex scoring functions.
Inglese
Macari, G., Toti, D., Del Moro, C., Polticelli, F., Fragment-based ligand-protein contact statistics: Application to docking simulations, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2019; 20 (10): 2499-2516. [doi:10.3390/ijms20102499] [http://hdl.handle.net/10807/163223]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/163223
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