Protein-ligand binding site detection as an alternative route to molecular docking and drug repurposing

• Autorzy: Toti D. , Macari G. , Polticelli F.

Identyfikatory

DOI

10.1515/bams-2018-0004

• Języki publikacji: EN

Abstrakty

EN

After the onset of the genomic era, the detection of ligand binding sites in proteins has emerged over the last few years as a powerful tool for protein function prediction. Several approaches, both sequence and structure based, have been developed, but the full potential of the corresponding tools has not been exploited yet. Here, we describe the development and classification of a large, almost exhaustive, collection of protein-ligand binding sites to be used, in conjunction with the Ligand Binding Site Recognition Application Web Application developed in our laboratory, as an alternative to virtual screening through molecular docking simulations to identify novel lead compounds for known targets. Ligand binding sites derived from the Protein Data Bank have been clustered according to ligand similarity, and given a known ligand, the binding mode of related ligands to the same target can be predicted. The collection of ligand binding sites contains more than 200,000 sites corresponding to more than 20,000 different ligands. Furthermore, the ligand binding sites of all Food and Drug Administration-approved drugs have been classified as well, allowing to investigate the possible binding of each of them (and related compounds) to a given target for drug repurposing and redesign initiatives. Sample usage cases are also described to demonstrate the effectiveness of this approach.

Słowa kluczowe

EN

drug repurposing; FDA-approved drugs; ligand binding site recognition; ligand binding sites

• Wydawca: Uniwersytet Jagielloński - Collegium Medicum ; Index Copernicus Sp. z o.o.
• Czasopismo: Bio-Algorithms and Med-Systems
• Rocznik: 2018
• Tom: Vol. 14, no. 2
• Strony: art. no. 20180004
• Opis fizyczny: Bibliogr. 36 poz., rys., tab.

Twórcy

autor

Toti D.

• Department of Sciences, Roma Tre University, 00146 Rome, Italy

autor

Macari G.

• Department of Sciences, Roma Tre University, 00146 Rome, Italy

autor

Polticelli F.

• Department of Sciences, Roma Tre University, 00146 Rome, Italy
• National Institute of Nuclear Physics, Roma Tre Section, 00146 Rome, Italy

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Uwagi

Opracowanie rekordu w ramach umowy 509/P-DUN/2018 ze środków MNiSW przeznaczonych na działalność upowszechniającą naukę (2019).