QSAR study of selective ligands for the thyroid hormone receptor β

In this paper, an accurate and reliable QSAR model of 87 selective ligands for the thyroid hormone receptor β 1 (TRβ1) was developed, based on theoretical molecular descriptors to predict the binding affinity of compounds with receptor. The structural characteristics of compounds were described wholly by a large amount of molecular structural descriptors calculated by DRAGON. Six most relevant structural descriptors to the studied activity were selected as the inputs of QSAR model by a robust optimization algorithm Genetic Algorithm. The built model was fully assessed by various validation methods, including internal and external validation, Y-randomization test, chemical applicability domain, and all the validations indicate that the QSAR model we proposed is robust and satisfactory. Thus, the built QSAR model can be used to fast and accurately predict the binding affinity of compounds (in the defined applicability domain) to TRβ1. At the same time, the model proposed could also identify and provide some insight into what structural features are related to the biological activity of these compounds and provide some instruction for further designing the new selective ligands for TRβ1 with high activity.