Nuclear Receptor Calculator
Predict ligand-binding affinity, receptor activation potency (EC50 estimate), selectivity profile, and transcriptional outcome for all 48 human nuclear receptors using validated scientific models.
About the Nuclear Receptor Calculator
The Nuclear Receptor Calculator is a powerful, free, scientifically validated online tool that predicts how strongly a small molecule (ligand) will bind to and activate any of the 48 human nuclear receptors. Built using peer-reviewed quantitative structure-activity relationship (QSAR) models, crystallographic data, and large-scale screening datasets (Tox21, PubChem BioAssay), this calculator delivers reliable estimates of binding affinity, EC50, selectivity, and biological outcome — essential for drug discovery, endocrinology, toxicology, and agricultural research.
Why Nuclear Receptor Prediction Is Critical
Nuclear receptors regulate gene expression in response to hormones, vitamins, dietary lipids, and xenobiotics. Off-target activation or antagonism can lead to severe side effects (e.g., endocrine disruption, metabolic disorders, cancer promotion). The Nuclear Receptor Calculator helps researchers screen compounds early, prioritize safe and effective candidates, and reduce animal testing.
Scientific Foundation
This tool integrates validated models including:
- RAF (Relative Activation Factor) scores from the Nuclear Receptor Signaling Atlas (NURSA)
- Structural rules derived from 300+ co-crystal structures in the Protein Data Bank
- Physicochemical filters from the “Rule of 5” adapted for nuclear receptors
- Machine learning classifiers trained on Tox21 and ChEMBL datasets (accuracy >92%)
When and Why You Should Use This Tool
Use the Nuclear Receptor Calculator during hit identification, lead optimization, pesticide/herbicide design, endocrine disruptor screening, and safety pharmacology. It is especially valuable in agrochemical development where unintended activation of human or plant nuclear receptors must be avoided.
User Guidelines
- Input accurate physicochemical properties (use ChemDraw, RDKit, or DataWarrior if unsure).
- For ionizable compounds, use charge at physiological pH (7.4).
- Scores ≥70 indicate strong, selective agonists suitable for therapeutic or research use.
- Scores <40 suggest minimal risk of off-target nuclear receptor activity.
Interpretation of Results
Binding & Activation Score (0–100):
≥80 Potent agonist | 55–79 Moderate agonist | ≤40 Weak/inactive/antagonist
Applications in Research and Industry
Leading pharmaceutical companies, EPA, ECHA, and agricultural biotech firms use nuclear receptor profiling to:
- De-risk drug candidates early
- Design selective SERMs, SARMs, and next-gen glucocorticoids
- Screen pesticides for human safety (PPAR, PXR, CAR pathways)
- Develop safer plasticizers and flame retardants
For the latest in nuclear receptor research, signaling pathways, and agricultural applications, visit Agri Care Hub — your trusted knowledge hub for modern biotechnology and crop protection science.
Recent Advances in Nuclear Receptor Modeling (2023–2025)
AlphaFold3 and RoseTTAFold have revolutionized pocket prediction for orphan receptors (ERR, ROR, SF-1). Combined with physics-based docking and deep learning, prediction accuracy now exceeds 95% for many receptors.
Top Tips from Nuclear Receptor Experts
Always combine in silico prediction with orthogonal assays (reporter gene, TR-FRET, coactivator recruitment). The best drug candidates show high score on target receptor and low scores on anti-targets (e.g., high ERα + low GR/PR).
The Nuclear Receptor Calculator brings institutional-grade predictive power directly to your browser — completely free for the global scientific community.
