The angiotensin (Ang) II type 1 receptor (AT1R) is the target for a widely used class of drugs named angiotensin receptor blockers (ARBs). Polymorphisms in the ARB binding site are known to alter affinity. Mutagenesis studies identifying the binding site are limited as the site can be distorted simply by altering helical rotation/position. Previously, we demonstrated that wild‐type (wt) opossum (o) AT1R does not bind ARBs. Therefore, we made a model of the human (h) AT1R and oAT1R based on the structure of the mu‐opioid receptor through an iterative process. The models were optimized using all atomic molecular dynamics (MD) simulation with explicit membrane bilayer and water solvent. Utilizing docking and MD simulations the ARB binding pocket was elucidated; currently, both K199 in the 3rd helix and the backbone near the lipid‐solvent interface appear to be involved in binding. Additionally, we cloned the hAT1R and made individual point mutations reflecting the differences between hAT1R and oAT1R. Each receptor was stably transfected into HEK cells and characterized to determine if there are alterations in Ang II signaling as well as ARB‐mediated inhibition of signaling. Iterations of modeling and wet lab work will refine the ARB binding site allowing for identification of ARB resistant patients. Grant Funding Source: T. Taylor was supported by an APS Frontiers in Physiology Fellowship.

Charge‐transfer‐Frequenzen der Tetracyanäthylen‐Komplexe (I)‐(III) bestätigen, daß die bei vertikaler σ‐π‐Konjugation auftretende Stabilisierung des nachbarlichen kationischen Zentrums sofort verschwindet, wenn die C‐Metall‐Bindung in der Ebene des aromatischen Ringes liegt.