Add like
Add dislike
Add to saved papers

Biased Agonist TRV027 Determinants in AT1R by Molecular Dynamics Simulations.

Functional selectivity is a phenomenon observed in G protein coupled-receptors (GPCR) in which intermediate active states conformations are stabilized by mutations or ligand binding, resulting in different sets of signaling pathways. Peptides capable of selectively activating β-arrestin, known as biased agonists, have already been characterized in vivo, and could correspond to a new therapeutic approach for cardiovascular diseases treatment. Despite biased agonism potential, the mechanism involved in selective signaling remains unclear. In this work, molecular dynamics simulations were employed to compare the conformational profile of AT1R crystal bond to angiotensin II (AngII), bond to the biased ligand TRV027 and in the apo form. Our results show that both ligands induce changes near the NPxxY motif in TM7 that are related to receptor activation. However, the biased ligand does not cause the rotamer toggle alternative positioning and displays an exclusive hydrogen bond pattern. Our work sheds light into biased agonism mechanism and will help future design of novel biased agonist for AT1R.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app