Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation
Background and purpose: Xanthohumol (Xn), a small molecule found in Humulus lupulus, has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation. Experimental approach: After ligand and pro...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-12-01
|
| Series: | Research in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/RPS.RPS_38_24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556313885114368 |
|---|---|
| author | Zohreh Gholizadeh Siahmazgi Shiva Irani Ali Ghiaseddin Fereshteh Soutodeh Zahra Gohari Jaber Afifeh Amirreza Pashapouryeganeh Hilda Samimi Mahmood Naderi Parviz Fallah Vahid Haghpanah |
| author_facet | Zohreh Gholizadeh Siahmazgi Shiva Irani Ali Ghiaseddin Fereshteh Soutodeh Zahra Gohari Jaber Afifeh Amirreza Pashapouryeganeh Hilda Samimi Mahmood Naderi Parviz Fallah Vahid Haghpanah |
| author_sort | Zohreh Gholizadeh Siahmazgi |
| collection | DOAJ |
| description | Background and purpose:
Xanthohumol (Xn), a small molecule found in Humulus lupulus, has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation.
Experimental approach:
After ligand and protein preparation, the best binding energy was determined using Autodock 4.2. Additionally, molecular dynamics simulations of the MEK1/2-Xn and BRaf-MEK1/2-Xn complexes were conducted using GROMACS 2022.1 software and compared to the complexes of MEK1/2-trametinib (Tra) and BRaf-MEK1/2-Tra.
Findings/Results:
The docking results revealed that the best binding energies for MEK1-Xn (-10.70 Kcal/mol), MEK2-Xn (-9.41 Kcal/mol), BRaf-MEK1-Xn (-10.91 Kcal/mol), and BRaf-MEK2-Xn (-8.54 Kcal/mol) were very close to those of the Tra complexes with their targets, MEK1 and MEK2. Furthermore, Xn was found to interact with serine 222 at the active site of these two kinases. The results of the molecular dynamics simulations also indicated that Xn induced changes in the secondary structure of the studied proteins. The root mean square of proteins and the mean radius of gyration showed significant fluctuations.
Conclusion and implications:
The findings of the study suggested that Xn, as a novel bioactive compound, potentially inhibits the MEK1/2 function in cancer cells. |
| format | Article |
| id | doaj-art-d9dd68008fa347afb6673ff7c7b89da9 |
| institution | Kabale University |
| issn | 1735-5362 1735-9414 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Research in Pharmaceutical Sciences |
| spelling | doaj-art-d9dd68008fa347afb6673ff7c7b89da92025-01-07T09:56:57ZengWolters Kluwer Medknow PublicationsResearch in Pharmaceutical Sciences1735-53621735-94142024-12-0119666968210.4103/RPS.RPS_38_24Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigationZohreh Gholizadeh SiahmazgiShiva IraniAli GhiaseddinFereshteh SoutodehZahra GohariJaber AfifehAmirreza PashapouryeganehHilda SamimiMahmood NaderiParviz FallahVahid HaghpanahBackground and purpose: Xanthohumol (Xn), a small molecule found in Humulus lupulus, has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation. Experimental approach: After ligand and protein preparation, the best binding energy was determined using Autodock 4.2. Additionally, molecular dynamics simulations of the MEK1/2-Xn and BRaf-MEK1/2-Xn complexes were conducted using GROMACS 2022.1 software and compared to the complexes of MEK1/2-trametinib (Tra) and BRaf-MEK1/2-Tra. Findings/Results: The docking results revealed that the best binding energies for MEK1-Xn (-10.70 Kcal/mol), MEK2-Xn (-9.41 Kcal/mol), BRaf-MEK1-Xn (-10.91 Kcal/mol), and BRaf-MEK2-Xn (-8.54 Kcal/mol) were very close to those of the Tra complexes with their targets, MEK1 and MEK2. Furthermore, Xn was found to interact with serine 222 at the active site of these two kinases. The results of the molecular dynamics simulations also indicated that Xn induced changes in the secondary structure of the studied proteins. The root mean square of proteins and the mean radius of gyration showed significant fluctuations. Conclusion and implications: The findings of the study suggested that Xn, as a novel bioactive compound, potentially inhibits the MEK1/2 function in cancer cells.https://journals.lww.com/10.4103/RPS.RPS_38_24active sitemek1mek2molecular dynamic simulationxanthohumol |
| spellingShingle | Zohreh Gholizadeh Siahmazgi Shiva Irani Ali Ghiaseddin Fereshteh Soutodeh Zahra Gohari Jaber Afifeh Amirreza Pashapouryeganeh Hilda Samimi Mahmood Naderi Parviz Fallah Vahid Haghpanah Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation Research in Pharmaceutical Sciences active site mek1 mek2 molecular dynamic simulation xanthohumol |
| title | Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation |
| title_full | Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation |
| title_fullStr | Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation |
| title_full_unstemmed | Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation |
| title_short | Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation |
| title_sort | exploring the inhibitory potential of xanthohumol on mek1 2 a molecular docking and dynamics simulation investigation |
| topic | active site mek1 mek2 molecular dynamic simulation xanthohumol |
| url | https://journals.lww.com/10.4103/RPS.RPS_38_24 |
| work_keys_str_mv | AT zohrehgholizadehsiahmazgi exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT shivairani exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT alighiaseddin exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT fereshtehsoutodeh exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT zahragohari exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT jaberafifeh exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT amirrezapashapouryeganeh exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT hildasamimi exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT mahmoodnaderi exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT parvizfallah exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation AT vahidhaghpanah exploringtheinhibitorypotentialofxanthohumolonmek12amoleculardockinganddynamicssimulationinvestigation |