title: Systemic QSAR and phenotypic virtual screening: chasing butterflies in drug discovery.
abstract: Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final outcomes and consequently prioritize those events, leading to a desired effect. Here, we introduce a new concept, 'Systemic Chemogenomics/Quantitative Structure-Activity Relationship (QSAR)'. To elaborate on the concept, relevant information surrounding it is addressed. The concept is challenged by implementing a systemic QSAR approach for phenotypic virtual screening (VS) of candidate ligands acting as neuroprotective agents in Parkinson's disease (PD). The results support the suitability of the approach for the phenotypic prioritization of drug candidates.
authors.affiliation: CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto 4169-007, Portugal. Electronic address: gmailkelcm@yahoo.es.
authors.forename: Maykel
authors.initials: M
authors.lastname: Cruz-Monteagudo
authors.affiliation: Department of Pharmacology, Miller School of Medicine and Center for Computational Science, University of Miami, Miami, FL 33136, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schürer
authors.affiliation: Instituto de Investigaciones Biomédicas (IIB), Universidad de Las Américas, 170513 Quito, Ecuador.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tejera
authors.affiliation: Sección Físico Química y Matemáticas, Departamento de Química, Universidad Técnica Particular de Loja, San Cayetano Alto S/N, EC1101608 Loja, Ecuador.
authors.forename: Yunierkis
authors.initials: Y
authors.lastname: Pérez-Castillo
authors.affiliation: Universidad Nacional Autónoma de México, Departamento de Farmacia, Facultad de Química, Avenida Universidad 3000, Mexico City, 04510, Mexico.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.affiliation: Departamento de Ciencias Naturales, Universidad Técnica Particular de Loja, Calle París S/N, EC1101608 Loja, Ecuador.
authors.forename: Aminael
authors.initials: A
authors.lastname: Sánchez-Rodríguez
authors.affiliation: CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto 4169-007, Portugal. Electronic address: fborges@fc.up.pt.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
mesh_terms: D055808:Drug Discovery; D023281:Genomics; D006801:Humans; D010641:Phenotype; D021281:Quantitative Structure-Activity Relationship