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In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575392/ https://www.ncbi.nlm.nih.gov/pubmed/36321085 http://dx.doi.org/10.1039/d2ra04226f |
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author | Jovanović, Jelena Đorović Antonijević, Marko Vojinović, Radiša Filipović, Nenad D. Marković, Zoran |
author_facet | Jovanović, Jelena Đorović Antonijević, Marko Vojinović, Radiša Filipović, Nenad D. Marković, Zoran |
author_sort | Jovanović, Jelena Đorović |
collection | PubMed |
description | Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treated with different medications, and promising results were shown by a relatively new medicament called Entresto. Results obtained from molecular docking and molecular dynamics simulations to examine the inhibitory capacity of Entresto are presented in this study. Parameters obtained by the molecular docking simulations show that both parts of Entresto (sacubitril (SAC) and valsartan (VAL)) interact with targeted proteins, and inhibit their physiological function. Simulations of molecular dynamics revealed some interesting inhibitory patterns. SAC was discovered to produce structural alterations in neprilysin by binding to it, reducing neprilysin's physiological activity. In addition to blocking the active site, SAC binding causes the enzyme's structure to become less compact over time, causing changes in its biochemical characteristics and preventing the enzyme from performing its biological function. Similar to SAC, VAL also causes deviations in the structure of angiotensin receptors. The angiotensin receptor GPCR (G-protein-coupled receptors) is immersed in the lipid bilayer, and changes in the tertiary structure are only visible through RMSD and RMSF, not by examining R(g). In this regard, MD simulations validated the results of molecular docking simulations, demonstrating that both SAC and VAL had inhibitory potential towards the neprilysin and angiotensin receptors, respectively. |
format | Online Article Text |
id | pubmed-9575392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-95753922022-10-31 In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor Jovanović, Jelena Đorović Antonijević, Marko Vojinović, Radiša Filipović, Nenad D. Marković, Zoran RSC Adv Chemistry Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treated with different medications, and promising results were shown by a relatively new medicament called Entresto. Results obtained from molecular docking and molecular dynamics simulations to examine the inhibitory capacity of Entresto are presented in this study. Parameters obtained by the molecular docking simulations show that both parts of Entresto (sacubitril (SAC) and valsartan (VAL)) interact with targeted proteins, and inhibit their physiological function. Simulations of molecular dynamics revealed some interesting inhibitory patterns. SAC was discovered to produce structural alterations in neprilysin by binding to it, reducing neprilysin's physiological activity. In addition to blocking the active site, SAC binding causes the enzyme's structure to become less compact over time, causing changes in its biochemical characteristics and preventing the enzyme from performing its biological function. Similar to SAC, VAL also causes deviations in the structure of angiotensin receptors. The angiotensin receptor GPCR (G-protein-coupled receptors) is immersed in the lipid bilayer, and changes in the tertiary structure are only visible through RMSD and RMSF, not by examining R(g). In this regard, MD simulations validated the results of molecular docking simulations, demonstrating that both SAC and VAL had inhibitory potential towards the neprilysin and angiotensin receptors, respectively. The Royal Society of Chemistry 2022-10-17 /pmc/articles/PMC9575392/ /pubmed/36321085 http://dx.doi.org/10.1039/d2ra04226f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Jovanović, Jelena Đorović Antonijević, Marko Vojinović, Radiša Filipović, Nenad D. Marković, Zoran In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title |
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title_full |
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title_fullStr |
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title_full_unstemmed |
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title_short |
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
title_sort | in silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575392/ https://www.ncbi.nlm.nih.gov/pubmed/36321085 http://dx.doi.org/10.1039/d2ra04226f |
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