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In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction

Nitric Oxide (NO) signaling pathway plays a vital role in various physiological and pathophysiological processes including vasodilation, neurogenesis, inflammation, translation and protein regulation. NO signaling pathway is associated with various diseases such as cardiovascular diseases, vision im...

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Autores principales: Malik, Abbeha, Iqbal, Muhammad Nasir, Ashraf, Sidrah, Khan, Muhammad Saleem, Shahzadi, Samar, Shafique, Muhammad Farhan, Sajid, Zureesha, Sajid, Muhammad, Sehgal, Sheikh Arslan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132633/
https://www.ncbi.nlm.nih.gov/pubmed/37099543
http://dx.doi.org/10.1371/journal.pone.0284993
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author Malik, Abbeha
Iqbal, Muhammad Nasir
Ashraf, Sidrah
Khan, Muhammad Saleem
Shahzadi, Samar
Shafique, Muhammad Farhan
Sajid, Zureesha
Sajid, Muhammad
Sehgal, Sheikh Arslan
author_facet Malik, Abbeha
Iqbal, Muhammad Nasir
Ashraf, Sidrah
Khan, Muhammad Saleem
Shahzadi, Samar
Shafique, Muhammad Farhan
Sajid, Zureesha
Sajid, Muhammad
Sehgal, Sheikh Arslan
author_sort Malik, Abbeha
collection PubMed
description Nitric Oxide (NO) signaling pathway plays a vital role in various physiological and pathophysiological processes including vasodilation, neurogenesis, inflammation, translation and protein regulation. NO signaling pathway is associated with various diseases such as cardiovascular diseases, vision impairment, hypertension and Alzheimer’s disease. Human Endothelial Nitric Oxide Synthase (eNOS) bound with calcium regulatory protein (calmodulin (CaM)) to produce NO which initiates cGMP pathway. The current study employs to screen the novel compounds against human eNOS independent of calcium regulatory protein (CaM). The current effort emphasized that the deficiency of CaM leads to dysfunction of cGMP signaling pathway. In this work, a hybrid approach of high-throughput virtual screening and comparative molecular docking studies followed by molecular dynamic simulation analyses were applied. The screening of top ranked two novel compounds against eNOS were reported that showed effective binding affinity, retrieved through the DrugBank and ZINC database libraries. Comparative molecular docking analyses revealed that Val-104, Phe-105, Gln-247, Arg-250, Ala-266, Trp-330, Tyr-331, Pro-334, Ala-335, Val-336, Tyr-357, Met-358, Thr-360, Glu-361, Ile-362, Arg-365, Asn-366, Asp-369, Arg-372, Trp-447 and Tyr-475 are potent residues for interactional studies. High-throughput virtual screening approach coupled with molecular dynamic simulation and drug likeness rules depicted that ZINC59677432 and DB00456 are potent compounds to target eNOS. In conclusion, the proposed compounds are potent against eNOS based on extensive in silico analyses. Overall, the findings of this study may be helpful to design therapeutic targets against eNOS.
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spelling pubmed-101326332023-04-27 In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction Malik, Abbeha Iqbal, Muhammad Nasir Ashraf, Sidrah Khan, Muhammad Saleem Shahzadi, Samar Shafique, Muhammad Farhan Sajid, Zureesha Sajid, Muhammad Sehgal, Sheikh Arslan PLoS One Research Article Nitric Oxide (NO) signaling pathway plays a vital role in various physiological and pathophysiological processes including vasodilation, neurogenesis, inflammation, translation and protein regulation. NO signaling pathway is associated with various diseases such as cardiovascular diseases, vision impairment, hypertension and Alzheimer’s disease. Human Endothelial Nitric Oxide Synthase (eNOS) bound with calcium regulatory protein (calmodulin (CaM)) to produce NO which initiates cGMP pathway. The current study employs to screen the novel compounds against human eNOS independent of calcium regulatory protein (CaM). The current effort emphasized that the deficiency of CaM leads to dysfunction of cGMP signaling pathway. In this work, a hybrid approach of high-throughput virtual screening and comparative molecular docking studies followed by molecular dynamic simulation analyses were applied. The screening of top ranked two novel compounds against eNOS were reported that showed effective binding affinity, retrieved through the DrugBank and ZINC database libraries. Comparative molecular docking analyses revealed that Val-104, Phe-105, Gln-247, Arg-250, Ala-266, Trp-330, Tyr-331, Pro-334, Ala-335, Val-336, Tyr-357, Met-358, Thr-360, Glu-361, Ile-362, Arg-365, Asn-366, Asp-369, Arg-372, Trp-447 and Tyr-475 are potent residues for interactional studies. High-throughput virtual screening approach coupled with molecular dynamic simulation and drug likeness rules depicted that ZINC59677432 and DB00456 are potent compounds to target eNOS. In conclusion, the proposed compounds are potent against eNOS based on extensive in silico analyses. Overall, the findings of this study may be helpful to design therapeutic targets against eNOS. Public Library of Science 2023-04-26 /pmc/articles/PMC10132633/ /pubmed/37099543 http://dx.doi.org/10.1371/journal.pone.0284993 Text en © 2023 Malik et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Malik, Abbeha
Iqbal, Muhammad Nasir
Ashraf, Sidrah
Khan, Muhammad Saleem
Shahzadi, Samar
Shafique, Muhammad Farhan
Sajid, Zureesha
Sajid, Muhammad
Sehgal, Sheikh Arslan
In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title_full In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title_fullStr In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title_full_unstemmed In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title_short In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction
title_sort in silico elucidation of potential drug targets against oxygenase domain of human enos dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132633/
https://www.ncbi.nlm.nih.gov/pubmed/37099543
http://dx.doi.org/10.1371/journal.pone.0284993
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