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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Biological Modeling and Simulation
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1414197

Molecular dynamic simulation reveals inhibiting impact of Rhein on Rac1, wild type and P29S mutation

Provisionally accepted
Negar Etebar Negar Etebar 1,2*Seyed Hootan Hamidi Seyed Hootan Hamidi 1,3Saghi Naderpour Saghi Naderpour 2*Omar Abouali Omar Abouali 4*Seyedeh Harir Hamidi Seyedeh Harir Hamidi 3,5*Alireza Zali Alireza Zali 1Mozhgan Alipour Mozhgan Alipour 1*Milad Rahimzadegan Milad Rahimzadegan 1*
  • 1 Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • 2 Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, Cyprus
  • 3 Acharya & BM Reddy College of Pharmacy, Bengaluru, Karnataka, India
  • 4 Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus
  • 5 Al-Ameen College of Pharmacy, Bengaluru, India

The final, formatted version of the article will be published soon.

    Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase belonging to the Rho family acting as a binary molecular switch regulating a number of cellular functions including cell adhesion and migration. Malfunctions due to the P29S mutation in Rac1 increase the stability of the activated form of Rac1. This sustained activation can drive aberrant cellular processes associated with cancer, such as cell proliferation, survival, and migration. Therefore, finding an inhibitor that can inhibit mutant form of the protein is very important. On the other hand, Rhein, a natural compound with diverse pharmacological properties, has been studied in relation to Rac1. While specific interactions between Rhein and Rac1 have not been examined. So, in this study, we investigated the potential of Rhein, a natural compound, as a Rac1 inhibitor in two forms wild type and P29S mutation using molecular dynamics simulations. Results indicated that P29S mutation led to structural changes in Rac1 protein that results in greater accessibility of the Rhein to the active site. Also binding energy of Rhein to mutant Rac1 was more negative than native protein. Therefore, it seems that the Rhein has a better inhibitory effect on the P29S mutated form of the Rac1 protein.

    Keywords: Cancer, Rac1, Rhein, P29S mutation, Molecular Dynamics Simulation

    Received: 23 Apr 2024; Accepted: 19 Jun 2024.

    Copyright: © 2024 Etebar, Hamidi, Naderpour, Abouali, Hamidi, Zali, Alipour and Rahimzadegan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Negar Etebar, Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Saghi Naderpour, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, Cyprus
    Omar Abouali, Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus
    Seyedeh Harir Hamidi, Acharya & BM Reddy College of Pharmacy, Bengaluru, Karnataka, India
    Mozhgan Alipour, Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Milad Rahimzadegan, Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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