title: Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson&#39;s Disease Dual Target Ligands.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Seccion Fisico Quimica y Matematicas, Departamento de Quimica, Universidad Tecnica Particular de Loja, San Cayetano Alto S/N, EC1101608 Loja, Ecuador.|Molecular Simulation and Drug Design Group, Centro de Bioactivos Quimicos (CBQ), Universidad Central "Marta Abreu" de Las Villas, Santa Clara, 54830, Cuba.
authors.forename: Yunierkis
authors.initials: Y
authors.lastname: Perez-Castillo
authors.affiliation: Molecular Simulation and Drug Design Group, Centro de Bioactivos Quimicos (CBQ), Universidad Central "Marta Abreu" de Las Villas, Santa Clara, 54830, Cuba.
authors.forename: Aliuska Morales
authors.initials: AM
authors.lastname: Helguera
authors.affiliation: REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
authors.forename: M Natalia D S
authors.initials: MNDS
authors.lastname: Cordeiro
authors.affiliation: Instituto de Investigaciones Biomedicas (IIB), Universidad de Las Americas, 170513 Quito, Ecuador.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tejera
authors.affiliation: Instituto de Investigaciones Biomedicas (IIB), Universidad de Las Americas, 170513 Quito, Ecuador.
authors.forename: Cesar
authors.initials: C
authors.lastname: Paz-Y-Mino
authors.affiliation: Departamento de Ciencias Naturales, Universidad Tecnica Particular de Loja, Calle Paris S/N, EC1101608 Loja, Ecuador.
authors.forename: Aminael
authors.initials: A
authors.lastname: Sanchez-Rodriguez
authors.affiliation: CIQUP/Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Porto 4169-007, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.affiliation: Instituto de Investigaciones Biomedicas (IIB), Universidad de Las Americas, 170513 Quito, Ecuador.|CIQUP/Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Porto 4169-007, Portugal.
authors.forename: Maykel
authors.initials: M
authors.lastname: Cruz-Monteagudo
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D011485:Protein Binding / Q000187:drug effects; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D043705:Receptor, Adenosine A2A; D008995:Monoamine Oxidase
keywords: Parkinson's disease; dual target ligands; molecular docking; scoring fusion.