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Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson's Disease Dual Target Ligands.
Perez-Castillo, Yunierkis; Helguera, Aliuska Morales; Cordeiro, M Natalia D S; Tejera, Eduardo; Paz-Y-Mino, Cesar; Sanchez-Rodriguez, Aminael; Borges, Fernanda; Cruz-Monteagudo, Maykel.
Afiliação
  • Perez-Castillo Y; Seccion Fisico Quimica y Matematicas, Departamento de Quimica, Universidad Tecnica Particular de Loja, San Cayetano Alto S/N, EC1101608 Loja, Ecuador.
  • Helguera AM; Molecular Simulation and Drug Design Group, Centro de Bioactivos Quimicos (CBQ), Universidad Central "Marta Abreu" de Las Villas, Santa Clara, 54830, Cuba.
  • Cordeiro MNDS; Molecular Simulation and Drug Design Group, Centro de Bioactivos Quimicos (CBQ), Universidad Central "Marta Abreu" de Las Villas, Santa Clara, 54830, Cuba.
  • Tejera E; REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
  • Paz-Y-Mino C; Instituto de Investigaciones Biomedicas (IIB), Universidad de Las Americas, 170513 Quito, Ecuador.
  • Sanchez-Rodriguez A; Instituto de Investigaciones Biomedicas (IIB), Universidad de Las Americas, 170513 Quito, Ecuador.
  • Borges F; Departamento de Ciencias Naturales, Universidad Tecnica Particular de Loja, Calle Paris S/N, EC1101608 Loja, Ecuador.
  • Cruz-Monteagudo M; CIQUP/Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Porto 4169-007, Portugal.
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.
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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 / Simulação de Acoplamento Molecular / 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
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

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 / Simulação de Acoplamento Molecular / 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