ReviewKeynoteSystemic QSAR and phenotypic virtual screening: chasing butterflies in drug discovery

•We introduce a new concept, the systemic chemogenomics/QSAR.•We address all the relevant information and knowledge surrounding the concept.•We propose an approach for phenotypic virtual screening.•We conduct a proof-of-concept experiment providing evidences on the validity of the approach.•We discuss the potential and limitations of the systemic chemogenomics/QSAR approach.

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.

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