Related Experiment Video
Updated: Jul 18, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Simulating alpha/beta selectivity at the human thyroid hormone receptor: consensus scoring using multidimensional
Angelo Vedani1, Martin Zumstein, Markus A Lill
1Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. angelo.vedani@unibas.ch
Abstract:
We present a consensus-scoring study on the human thyroid hormone receptor alpha and beta using two receptor-modeling concepts (software Quasar and Raptor) that are based on multidimensional QSAR and allow for the explicit simulation of induced fit. The binding mode of 82 agonists and indirect antagonists, spanning an activity range of seven orders of magnitude in K(i), was identified through flexible docking to the respective X-ray crystal structures (Yeti software) and represented by a 4D data set with up to four conformations per compound. The receptor surrogates for the thyroid alpha receptor converged at a cross-validated r(2) of 0.846/0.919 (64 training compounds; for Quasar and Raptor, respectively) and yielded a predictive r(2) of 0.812/0.814 (18 test compounds); the models for the thyroid beta receptor resulted in a cross-validated r(2) of 0.823/0.909 and a predictive r(2) of 0.665/0.796, respectively. Consensus was achieved as, on average, the calculated activities of the training set differ only by a factor of 2.2 in K(i) and those of the test set by a factor of 2.8 when predicted by Quasar and Raptor, respectively.
Related Concept Videos
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Quantitative Aspects of Drug-Receptor Interaction
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with one...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
