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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/5/709 |
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| author | Dakshinamurthy Sivakumar Sathishkumar Mudedla Seonghun Jang Hyunjun Kim Hyunjin Park Yonwon Choi Joongyo Oh Sangwook Wu |
| author_facet | Dakshinamurthy Sivakumar Sathishkumar Mudedla Seonghun Jang Hyunjun Kim Hyunjin Park Yonwon Choi Joongyo Oh Sangwook Wu |
| author_sort | Dakshinamurthy Sivakumar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T11:33:40Z |
| format | Article |
| id | doaj.art-68b93a66ddb74f04bb963e1f3fef74b5 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T11:33:40Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-68b93a66ddb74f04bb963e1f3fef74b52023-11-21T19:02:31ZengMDPI AGBiomolecules2218-273X2021-05-0111570910.3390/biom11050709Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn SystemsDakshinamurthy Sivakumar0Sathishkumar Mudedla1Seonghun Jang2Hyunjun Kim3Hyunjin Park4Yonwon Choi5Joongyo Oh6Sangwook Wu7R&D Center, Pharmcadd, 221, 17 APEC-ro, Haeundae-gu, Busan 48060, KoreaR&D Center, Pharmcadd, 221, 17 APEC-ro, Haeundae-gu, Busan 48060, KoreaR&D Center, Pharmcadd, 221, 17 APEC-ro, Haeundae-gu, Busan 48060, KoreaR&D Center, Huons co. Ltd., Ansan-si 15588, KoreaR&D Center, Huons co. Ltd., Ansan-si 15588, KoreaR&D Center, Huons co. Ltd., Ansan-si 15588, KoreaR&D Center, Huons co. Ltd., Ansan-si 15588, KoreaR&D Center, Pharmcadd, 221, 17 APEC-ro, Haeundae-gu, Busan 48060, KoreaPDE9 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.https://www.mdpi.com/2218-273X/11/5/709selective inhibitorsPDE9molecular dynamicsmetal complexesBAY73-6691 |
| spellingShingle | Dakshinamurthy Sivakumar Sathishkumar Mudedla Seonghun Jang Hyunjun Kim Hyunjin Park Yonwon Choi Joongyo Oh Sangwook Wu Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems Biomolecules selective inhibitors PDE9 molecular dynamics metal complexes BAY73-6691 |
| 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 | selective inhibitors PDE9 molecular dynamics metal complexes BAY73-6691 |
| url | https://www.mdpi.com/2218-273X/11/5/709 |
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