Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson's Disease Dual Target Ligands.
Curr Neuropharmacol
; 15(8): 1107-1116, 2017 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-28067172
BACKGROUND: Virtual methodologies have become essential components of the drug discovery pipeline. Specifically, structure-based drug design methodologies exploit the 3D structure of molecular targets to discover new drug candidates through molecular docking. Recently, dual target ligands of the Adenosine A2A Receptor and Monoamine Oxidase B enzyme have been proposed as effective therapies for the treatment of Parkinson's disease. METHODS: In this paper we propose a structure-based methodology, which is extensively validated, for the discovery of dual Adenosine A2A Receptor/Monoamine Oxidase B ligands. This methodology involves molecular docking studies against both receptors and the evaluation of different scoring functions fusion strategies for maximizing the initial virtual screening enrichment of known dual ligands. RESULTS: The developed methodology provides high values of enrichment of known ligands, which outperform that of the individual scoring functions. At the same time, the obtained ensemble can be translated in a sequence of steps that should be followed to maximize the enrichment of dual target Adenosine A2A Receptor antagonists and Monoamine Oxidase B inhibitors. CONCLUSION: Information relative to docking scores to both targets have to be combined for achieving high dual ligands enrichment. Combining the rankings derived from different scoring functions proved to be a valuable strategy for improving the enrichment relative to single scoring function in virtual screening experiments.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Receptor A2A de Adenosina
/
Antagonistas do Receptor A2 de Adenosina
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Simulação de Acoplamento Molecular
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Monoaminoxidase
/
Inibidores da Monoaminoxidase
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Neuropharmacol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Equador
País de publicação:
Emirados Árabes Unidos