Open (Quantitative) Structure-activity/property Relationship App
Quantitative structure–activity/property relationship (QSAR/QSPR) models provide predictions of chemical activity that can augment non-animal approaches for predicting toxicity. However, the performance of QSAR models highly depends on the quality of the data and modeling methodologies used.
The Open (Quantitative) Structure-activity/property Relationship App (OPERA) (Mansouri et al. 2018) was created to provide robust QSAR/QSPR models for chemical properties of environmental interest that can be used for regulatory purposes. OPERA is a free and open-source/open-data suite of QSAR models providing predictions for physicochemical properties, environmental fate parameters, and toxicity endpoints. All OPERA models were built on curated data and QSAR-ready chemical structures standardized using an open-source workflow (Mansouri et al. 2016).
OPERA is an ongoing collaboration between NICEATM and EPA. Additions to OPERA include predictions for:
- Estrogenic activity from the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) (Mansouri et al. 2016).
- Androgenic activity from the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) (Mansouri et al. 2020).
- Acute oral systemic toxicity from the Collaborative Acute Toxicity Modeling Suite (CATMoS) (Mansouri et al. 2021)
- Physicochemical properties such as acid dissociation constant (pKa) and octanol-water dissociation coefficient (logD) (Mansouri et al. 2019).
Other endpoints predicted by OPERA models include:
- Physicochemical parameters such as octanol-water partition coefficient (logP), water solubility, and melting point.
- Parameters for inputs into pharmacokinetic models, such as hepatic clearance, plasma fraction unbound, and intestinal cell permeability.
- Ecotoxicity parameters such as fish bioconcentration factor, soil adsorption coefficient, and biodegradability.
Recent updates to OPERA were discussed in a poster (Mansouri et al.) presented at the 2022 annual meeting of the Society of Toxicology.
OPERA predictions of toxicity and physicochemical properties are available through the Integrated Chemical Environment (ICE) and the EPA CompTox Chemicals Dashboard. For local use, the OPERA application can be downloaded from the NIEHS GitHub repository. Command-line and graphical user interface versions are available for Windows and Linux operating systems. OPERA is also now available as an extension to QSAR Toolbox, a tool co-developed by ECHA and OECD to support animal-free chemical hazard assessment.