Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson's Disease Dual Target Ligands

Title:Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson's Disease Dual Target Ligands

Volume: 15 Issue: 8

Author(s): Yunierkis Perez-Castillo, Aliuska Morales Helguera, M.Natalia D. S. Cordeiro, Eduardo Tejera, Cesar Paz-y-Mino, Aminael Sanchez-Rodriguez, Fernanda Borges*Maykel Cruz-Monteagudo

Affiliation:

• CIQUP/Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Porto 4169-007,Portugal

Keywords: Parkinson's disease, dual target ligands, molecular docking, scoring fusion.

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.

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.

Cite this article as:

Perez-Castillo Yunierkis, Helguera Morales Aliuska, Cordeiro D. S. M.Natalia , Tejera Eduardo, Paz-y-Mino Cesar, Sanchez-Rodriguez Aminael, Borges Fernanda*, Cruz-Monteagudo Maykel, Fusing Docking Scoring Functions Improves the Virtual Screening Performance for Discovering Parkinson's Disease Dual Target Ligands, Current Neuropharmacology 2017; 15 (8) . https://dx.doi.org/10.2174/1570159X15666170109143757