Thyroid hormone interactions with DMPC bilayers. A molecular dynamics study.

The structure and dynamics of thyroxine (T4), distal and proximal conformers of 3',3,5-triiodo-l-thyronine (T3d and T3p), and 3,5-diiodo-l-thyronine (T2) upon interaction with DMPC membranes were analyzed by means of molecular dynamics simulations. The locations, the more stable orientations, and the structural changes adopted by the hormones in the lipid medium evidence that the progressive iodine substitution on the beta ring lowers both the possibility of penetration and the transversal mobility in the membrane. However, the results obtained for T3d show that the number of iodine atoms in the molecule is not the only relevant factor in the hormone behavior but also the orientation of the single iodine substitution. The electrostatic interactions between the zwitterion group of the hormones with specific groups in the hydrophilic region of the membrane as well as the organization of the alkyl chains around the aromatic beta ring of the hormone were evaluated in terms of several radial distribution functions.