title: QSAR Modeling is not "Push a Button and Find a Correlation": A Case Study of Toxicity of (Benzo-)triazoles on Algae.
abstract: A case study of toxicity of (benzo)triazoles ((B)TAZs) to the algae Pseudokirchneriella subcapitata is used to discuss some problems and solutions in QSAR modeling, particularly in the environmental context. The relevance of data curation (not only of experimental data, but also of chemical structures and input formats for the calculation of molecular descriptors), the crucial points of QSAR model validation and the potential application for new chemicals (internal robustness, exclusion of chance correlation, external predictivity, applicability domain) are described, while developing MLR-OLS models based on molecular descriptors, calculated by various QSAR software tools (commercial DRAGON, free PaDEL-Descriptor and QSPR-THESAURUS). Additionally, the utility of consensus models is highlighted. This work summarizes a methodology for a rigorous statistical approach to obtain reliable QSAR predictions, also for a large number of (B)TAZs in the ECHA preregistration list of REACH (even if starting from limited experimental data availability), and has evidenced some ambiguities and discrepancies related to SMILES notations from different databases; furthermore it highlighted some general problems related to QSAR model generation and was useful in the implementation of the PaDEL-Descriptor software.
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100, Varese, Italy, http://www.qsar.it. paola.gramatica@uninsubria.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Gramatica
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100, Varese, Italy, http://www.qsar.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cassani
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100, Varese, Italy, http://www.qsar.it.|Present Address: Guru Ghasidas University, Bilaspur, Koni, India.
authors.forename: Partha Pratim
authors.initials: PP
authors.lastname: Roy
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100, Varese, Italy, http://www.qsar.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Kovarich
authors.affiliation: Department of Pharmacy, Pharmaceutical Data Exploration Laboratory, National University of Singapore, Singapore.
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Yap
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100, Varese, Italy, http://www.qsar.it.
authors.forename: Ester
authors.initials: E
authors.lastname: Papa
keywords: Chemical structure pitfalls; Molecular descriptors; QSAR tutorial; REACH; SMILES; Triazole algae toxicity; Validation