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Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine
Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in , has inhibitory act...
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| Published in: | Life (Basel, Switzerland) Switzerland), 2023-02, Vol.13 (2), p.578 |
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| Main Authors: | , , , , , |
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| container_issue | 2 |
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| creator | Kobayashi, Ayame Nakajima, Motokuni Noguchi, Yoh Morikawa, Ryota Matsuo, Yukiko Takasu, Masako |
| description | Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in
, has inhibitory activity for PDE5.
contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity. |
| doi_str_mv | 10.3390/life13020578 |
| format | article |
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, has inhibitory activity for PDE5.
contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.</description><identifier>ISSN: 2075-1729</identifier><identifier>EISSN: 2075-1729</identifier><identifier>DOI: 10.3390/life13020578</identifier><identifier>PMID: 36836935</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alkaloids ; Alzheimer's disease ; Care and treatment ; Chemical properties ; Communication ; Comparative analysis ; Energy ; Enzymes ; evodiamine ; Health aspects ; Hydrogen bonds ; Hydrolases ; Kinases ; Medicinal plants ; Memory ; Methods ; Molecular dynamics ; molecular dynamics simulation ; Molecular simulation ; natural product ; Nervous system diseases ; Neurodegenerative diseases ; Neurological diseases ; Optimization ; PDE5 ; Pharmacology, Experimental ; Phosphorylation ; Proteins ; Simulation</subject><ispartof>Life (Basel, Switzerland), 2023-02, Vol.13 (2), p.578</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-479602c00d5e80f7f094d8bd2e90f2e8bccff1eda45401b103e5fdb0293a3eb03</citedby><cites>FETCH-LOGICAL-c579t-479602c00d5e80f7f094d8bd2e90f2e8bccff1eda45401b103e5fdb0293a3eb03</cites><orcidid>0000-0001-9958-9756</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2779513963/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2779513963?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36836935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kobayashi, Ayame</creatorcontrib><creatorcontrib>Nakajima, Motokuni</creatorcontrib><creatorcontrib>Noguchi, Yoh</creatorcontrib><creatorcontrib>Morikawa, Ryota</creatorcontrib><creatorcontrib>Matsuo, Yukiko</creatorcontrib><creatorcontrib>Takasu, Masako</creatorcontrib><title>Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine</title><title>Life (Basel, Switzerland)</title><addtitle>Life (Basel)</addtitle><description>Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in
, has inhibitory activity for PDE5.
contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.</description><subject>Alkaloids</subject><subject>Alzheimer's disease</subject><subject>Care and treatment</subject><subject>Chemical properties</subject><subject>Communication</subject><subject>Comparative analysis</subject><subject>Energy</subject><subject>Enzymes</subject><subject>evodiamine</subject><subject>Health aspects</subject><subject>Hydrogen bonds</subject><subject>Hydrolases</subject><subject>Kinases</subject><subject>Medicinal plants</subject><subject>Memory</subject><subject>Methods</subject><subject>Molecular dynamics</subject><subject>molecular dynamics simulation</subject><subject>Molecular simulation</subject><subject>natural product</subject><subject>Nervous system diseases</subject><subject>Neurodegenerative diseases</subject><subject>Neurological diseases</subject><subject>Optimization</subject><subject>PDE5</subject><subject>Pharmacology, Experimental</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Simulation</subject><issn>2075-1729</issn><issn>2075-1729</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptklFvFCEQxzdGY5vaN5_NJr5o4tUBlgVeTJrrqZfUaKw-ExaGK5fd5Vx2m_bby_VqvTPCA8Pwm__AMEXxksAZYwret8EjYUCBC_mkOKYg-IwIqp7u2UfFaUpryKPmpJbV8-KI1ZLVivHjYv4ltmin1gzlxV1vumBTeRW67BhD7Mvoy_Eay3nsNi3ebrffLha8NL0rFzfRhRzQ44vimTdtwtOH9aT4-XHxY_55dvn103J-fjmzXKhxVglVA7UAjqMELzyoysnGUVTgKcrGWu8JOlPxCkhDgCH3rgGqmGHYADspljtdF81ab4bQmeFORxP0vSMOK22GMdgWtXTG174xDeeycoYqbzwK1lACtVGiylofdlqbqenQWezHwbQHoocnfbjWq3ijlaolBZYF3jwIDPHXhGnUXUgW29b0GKekqZAAkkqyzfX6H3Qdp6HPpcqUUJwwVbO_1MrkB4Tex5zXbkX1ueDAKmD39z77D5Wnw_x3sUcfsv8g4O1BQGZGvB1XZkpJL6--H7LvdqwdYkoD-sd6ENDbftP7_ZbxV_s1fIT_dBf7DYl1zX8</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Kobayashi, Ayame</creator><creator>Nakajima, Motokuni</creator><creator>Noguchi, Yoh</creator><creator>Morikawa, Ryota</creator><creator>Matsuo, Yukiko</creator><creator>Takasu, Masako</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9958-9756</orcidid></search><sort><creationdate>20230201</creationdate><title>Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine</title><author>Kobayashi, Ayame ; Nakajima, Motokuni ; Noguchi, Yoh ; Morikawa, Ryota ; Matsuo, Yukiko ; Takasu, Masako</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-479602c00d5e80f7f094d8bd2e90f2e8bccff1eda45401b103e5fdb0293a3eb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alkaloids</topic><topic>Alzheimer's disease</topic><topic>Care and treatment</topic><topic>Chemical properties</topic><topic>Communication</topic><topic>Comparative analysis</topic><topic>Energy</topic><topic>Enzymes</topic><topic>evodiamine</topic><topic>Health aspects</topic><topic>Hydrogen bonds</topic><topic>Hydrolases</topic><topic>Kinases</topic><topic>Medicinal plants</topic><topic>Memory</topic><topic>Methods</topic><topic>Molecular dynamics</topic><topic>molecular dynamics simulation</topic><topic>Molecular simulation</topic><topic>natural product</topic><topic>Nervous system diseases</topic><topic>Neurodegenerative diseases</topic><topic>Neurological diseases</topic><topic>Optimization</topic><topic>PDE5</topic><topic>Pharmacology, Experimental</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Simulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kobayashi, Ayame</creatorcontrib><creatorcontrib>Nakajima, Motokuni</creatorcontrib><creatorcontrib>Noguchi, Yoh</creatorcontrib><creatorcontrib>Morikawa, Ryota</creatorcontrib><creatorcontrib>Matsuo, Yukiko</creatorcontrib><creatorcontrib>Takasu, Masako</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Life (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kobayashi, Ayame</au><au>Nakajima, Motokuni</au><au>Noguchi, Yoh</au><au>Morikawa, Ryota</au><au>Matsuo, Yukiko</au><au>Takasu, Masako</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine</atitle><jtitle>Life (Basel, Switzerland)</jtitle><addtitle>Life (Basel)</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>13</volume><issue>2</issue><spage>578</spage><pages>578-</pages><issn>2075-1729</issn><eissn>2075-1729</eissn><abstract>Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in
, has inhibitory activity for PDE5.
contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36836935</pmid><doi>10.3390/life13020578</doi><orcidid>https://orcid.org/0000-0001-9958-9756</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Life (Basel, Switzerland), 2023-02, Vol.13 (2), p.578 |
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| subjects | Alkaloids Alzheimer's disease Care and treatment Chemical properties Communication Comparative analysis Energy Enzymes evodiamine Health aspects Hydrogen bonds Hydrolases Kinases Medicinal plants Memory Methods Molecular dynamics molecular dynamics simulation Molecular simulation natural product Nervous system diseases Neurodegenerative diseases Neurological diseases Optimization PDE5 Pharmacology, Experimental Phosphorylation Proteins Simulation |
| title | Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine |
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