Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus.
The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokineti...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0280847 |
| _version_ | 1811169455944761344 |
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| author | Tejaswini Maradesha Reshma Mary Martiz Shashank M Patil Ashwini Prasad Abdullatif Taha Babakr Ekaterina Silina Victor Stupin Raghu Ram Achar Ramith Ramu |
| author_facet | Tejaswini Maradesha Reshma Mary Martiz Shashank M Patil Ashwini Prasad Abdullatif Taha Babakr Ekaterina Silina Victor Stupin Raghu Ram Achar Ramith Ramu |
| author_sort | Tejaswini Maradesha |
| collection | DOAJ |
| description | The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3'-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal's free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus. |
| first_indexed | 2024-04-10T16:42:40Z |
| format | Article |
| id | doaj.art-e2c33ce09c534aafbae1d7fbecd34b38 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T16:42:40Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e2c33ce09c534aafbae1d7fbecd34b382023-02-08T05:31:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e028084710.1371/journal.pone.0280847Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus.Tejaswini MaradeshaReshma Mary MartizShashank M PatilAshwini PrasadAbdullatif Taha BabakrEkaterina SilinaVictor StupinRaghu Ram AcharRamith RamuThe current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3'-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal's free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus.https://doi.org/10.1371/journal.pone.0280847 |
| spellingShingle | Tejaswini Maradesha Reshma Mary Martiz Shashank M Patil Ashwini Prasad Abdullatif Taha Babakr Ekaterina Silina Victor Stupin Raghu Ram Achar Ramith Ramu Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. PLoS ONE |
| title | Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. |
| title_full | Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. |
| title_fullStr | Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. |
| title_full_unstemmed | Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. |
| title_short | Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus. |
| title_sort | integrated network pharmacology and molecular modeling approach for the discovery of novel potential mapk3 inhibitors from whole green jackfruit flour targeting obesity linked diabetes mellitus |
| url | https://doi.org/10.1371/journal.pone.0280847 |
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