Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems

PDE9 inhibitors have been studied to validate their potential to treat diabetes, neurodegenerative disorders, cardiovascular diseases, and erectile dysfunction. In this report, we have selected highly potent previously reported selective PDE9 inhibitors BAY73-6691R, BAY73-6691S, 28r, 28s, 3r, 3s, PF...

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Autores principales: Sivakumar, Dakshinamurthy, Mudedla, Sathishkumar, Jang, Seonghun, Kim, Hyunjun, Park, Hyunjin, Choi, Yonwon, Oh, Joongyo, Wu, Sangwook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151263/
https://www.ncbi.nlm.nih.gov/pubmed/34068780
http://dx.doi.org/10.3390/biom11050709
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author Sivakumar, Dakshinamurthy
Mudedla, Sathishkumar
Jang, Seonghun
Kim, Hyunjun
Park, Hyunjin
Choi, Yonwon
Oh, Joongyo
Wu, Sangwook
author_facet Sivakumar, Dakshinamurthy
Mudedla, Sathishkumar
Jang, Seonghun
Kim, Hyunjun
Park, Hyunjin
Choi, Yonwon
Oh, Joongyo
Wu, Sangwook
author_sort Sivakumar, Dakshinamurthy
collection PubMed
description PDE9 inhibitors have been studied to validate their potential to treat diabetes, neurodegenerative disorders, cardiovascular diseases, and erectile dysfunction. In this report, we have selected highly potent previously reported selective PDE9 inhibitors BAY73-6691R, BAY73-6691S, 28r, 28s, 3r, 3s, PF-0447943, PF-4181366, and 4r to elucidate the differences in their interaction patterns in the presence of different metal systems such as Zn/Mg, Mg/Mg, and Zn/Zn. The initial complexes were generated by molecular docking followed by molecular dynamics simulation for 100 ns in triplicate for each system to understand the interactions’ stability. The results were carefully analyzed, focusing on the ligands’ non-bonded interactions with PDE9 in different metal systems.
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spelling pubmed-81512632021-05-27 Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems Sivakumar, Dakshinamurthy Mudedla, Sathishkumar Jang, Seonghun Kim, Hyunjun Park, Hyunjin Choi, Yonwon Oh, Joongyo Wu, Sangwook Biomolecules Article PDE9 inhibitors have been studied to validate their potential to treat diabetes, neurodegenerative disorders, cardiovascular diseases, and erectile dysfunction. In this report, we have selected highly potent previously reported selective PDE9 inhibitors BAY73-6691R, BAY73-6691S, 28r, 28s, 3r, 3s, PF-0447943, PF-4181366, and 4r to elucidate the differences in their interaction patterns in the presence of different metal systems such as Zn/Mg, Mg/Mg, and Zn/Zn. The initial complexes were generated by molecular docking followed by molecular dynamics simulation for 100 ns in triplicate for each system to understand the interactions’ stability. The results were carefully analyzed, focusing on the ligands’ non-bonded interactions with PDE9 in different metal systems. MDPI 2021-05-10 /pmc/articles/PMC8151263/ /pubmed/34068780 http://dx.doi.org/10.3390/biom11050709 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sivakumar, Dakshinamurthy
Mudedla, Sathishkumar
Jang, Seonghun
Kim, Hyunjun
Park, Hyunjin
Choi, Yonwon
Oh, Joongyo
Wu, Sangwook
Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title_full Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title_fullStr Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title_full_unstemmed Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title_short Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems
title_sort computational study on selective pde9 inhibitors on pde9-mg/mg, pde9-zn/mg, and pde9-zn/zn systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151263/
https://www.ncbi.nlm.nih.gov/pubmed/34068780
http://dx.doi.org/10.3390/biom11050709
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