Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors

Li Fang; Mingxian Geng; Chunlei Liu; Ji Wang; Weihong Min; Jingsheng Liu

doi:10.1371/journal.pone.0215609

Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors

PLoS One. 2019 Apr 18;14(4):e0215609. doi: 10.1371/journal.pone.0215609. eCollection 2019.

Authors

Li Fang^{1

2}, Mingxian Geng^{1

2

3}, Chunlei Liu^{1

2}, Ji Wang^{1

2}, Weihong Min^{1

2}, Jingsheng Liu^{1

2}

Affiliations

¹ College of Food Science and Engineering, Jilin Agricultural University, Changchun, China.
² National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun, China.
³ Changchun Vocational Institute of Technology, Changchun, China.

Abstract

Angiotensin-I converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase involved in regulating blood pressure via the kallikrein-kininand renin-angiotensin-aldosterone complex. Therefore, ACE is a key drug target for the treatment of cardiovascular system diseases. At present many works are focus on searching for new inhibitory peptides of ACE to control the blood pressure. In order to exploit the interactions between ACE and its inhibitors, molecular dynamics simulations were used. The results showed that (a) the secondary structures of the three inhibitor-protein complexes did not change significantly; (b) root-mean-square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA) values of Leu-Ile-Val-Thr (LIVT)-ACE complexes were significantly higher than that of other systems; (c) the backbone movement of LIVT was vigorous in Asp300-Val350, compared with that in Tyr-Leu-Val-Pro-His (YLVPH) and Tyr-Leu-Val-Arg(YLVR), as shown by the center-of-mass distance; and (d) the backbone movement of Asp300-Val350 may contribute to the interaction between ACE and its inhibitors. Our theoretical results will be helpful to further the design of specific inhibitors of ACE.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemistry*
Computer Simulation*
Humans
Models, Molecular*
Peptides / chemistry*
Peptidyl-Dipeptidase A / chemistry*
Protein Domains
Structure-Activity Relationship

Substances

Angiotensin-Converting Enzyme Inhibitors
Peptides
Peptidyl-Dipeptidase A

Grants and funding

This study was supported by the National High Technology Research and Development Program of China (863 Program), grant/award number: 2013AA102206-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.