Effects of Angiotensin 1-7 Binding on the Dynamics of Human MAS Proto-Oncogene, GPCR: A Molecular Dynamics Study

Abstract

The understanding of the connections between Angiotensin peptides with the receptors in the Renin-angiotensin system (RAS) is not clear yet. The ACE2/Ang (1-7)/MAS axis, commonly referred to as the protective arm of the RAS, plays a crucial role in maintaining homeostasis within the cardiovascular system. Angiotensin 1-7 (Ang 1-7) is a heptapeptide an integral part of the protective arm of RAS and acts as a ligand binding to the MAS receptor. Understanding the signaling system of the ACE2/Ang (1-7)/MAS axis, which occupies an important place in the RAS, can be considered a serious putative target for the development of new cardiovascular and cancer drugs. It is very important to understand whether the Ang (1-7) ligand binds stably to MAS and, if so, how this affects the dynamics of the receptor. Therefore, we investigated how Ang (1-7) binding affects the stability and communication of the MAS receptor by utilizing molecular dynamics (MD) simulations and various computational techniques. Results indicated that Ang (1-7) was stably bonded to the MAS receptor over the 300[Formula: see text]ns simulation period. It was also observed that ligand binding caused a reduction in the fluctuations of the MAS residues. Major changes include a reduction in flexibility of the N-terminal domain, ICL1, ECL1, ECL2, ECL3, TM6 and C-terminal domain residues. Our findings presented in this study may provide a contribution to future studies seeking to gain a deeper understanding of the role of Ang (1-7) interaction with the MAS receptor in the RAS.