Implications of an improved model of the TSH receptor transmembrane domain (TSHR-TMD -TRIO) Abstract: The TSH receptor is a GPCR Group A family member with seven transmembrane helices. We generated three new models of its entire transmembrane region using a 600 ns molecular simulation. The simulation started from our previously published model which we have now revised by also modeling the intracellular loops and the C-terminal tail, adding internal waters and embedding it into a lipid bilayer with a water layer and with ions added to complete the system. We have named this model TSHR-TMD - TRIO since three representative dominant structures were then extracted from the simulation trajectory and compared with the original model. These structures each showed small but significant changes in the relative positions of the helices. The three models were also used as targets to dock a set of small molecules that are known active compounds including a new TSHR antagonist (BT362), which confirmed the appropriateness of the model with some small molecules showing significant preference for one or other of the structures.