Unraveling the M1R Protein of Monkeypox Virus: An Integrated Struc- tural Bioinformatics, Immunological Profiling, and Molecular Dynam- ics Simulation Approach

Cena  Aram; Kiarash  Saleki; Amirreza  Mazloomi; Maryam  Barancheshmeh; Nima  Rezaei

doi:10.18502/igj.v8i4.20099

Cena Aram Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
Kiarash Saleki Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Amirreza Mazloomi Student Research Committee, Babol University of Medical Sciences, Babol, Iran
Maryam Barancheshmeh Universal Scientific Education and Research Network (USERN), Nowshahr, Iran
Nima Rezaei Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/igj.v8i4.20099

Keywords: Monkeypox; Molecular Mechanics, Molecular Dynamic Simulation; M1R Protein; Structural Immunology

Abstract

Background: Monkeypox virus (MPXV) is a zoonotic pathogen that affects both humans and animals, posing a significant publichealth concern due to its emergence and circulation. The structural dynamics and features of several MPXV proteins, includingM1R, are not completely studied.

Methods: This experiment focuses on the prediction and analysis of the secondary and tertiary constructs for the M1R protein.Briefly, its amino acid sequence was collected from the UniProt database. A wide range of in silico approaches were employed,including ProtParam, SOPMA, PSIPRED, CD Search, GalaxyTMB, Robetta, I-TASSER, and GROMACS, in order to explore thephysicochemical properties, structural features, and functional insights of the M1R protein. The tertiary structure models wereevaluated to detect the most reliable solution, which was then used for Immunoinformatics analyses such as MHC I/II and B-cellepitope prediction using the IEDB and Ellipro tools, respectively. Epitopes from the M1R protein were evaluated based on anti-genicity, affinity of binding, along solubility. Furthermore, active sites were forecast by the CASTp v3.0 tool.

Results: Physicochemical calculations indicate that M1R had favorable thermostability and hydrophilic features. Structural anal-yses suggested that M1R is a lipid membrane protein component of DNA viruses, suggesting it as a robust antigenic target. Im-munogenicity analyses indicated it as a potentially suitable target for immunogenic protein design. As well, molecular dynamicssimulations (MDS) were carried out for 100-ns using an all-atom forcefield. Analysis of various molecular dynamics parametersof M1R throughout the MDS trajectory, including RMSD, RMSF, radius of gyration (Rg), and solvent accessible surface area(SASA), indicated good stability of the M1R and unveiled important molecular dynamics characteristics such as the flexibility ofcertain protein regions. Multiple epitopes were detected in our experiment, with 12 B-cell epitopes identified using the Robettamodel and 6 B-cell epitopes predicted by the Galaxy model, alongside 3 MHC-I and 3 MHC-II epitopes, which scored favorably.

Conclusion: The results of the present computational analysis provide clues to unleash the potential of M1R as an immunother apy target for the development of antiviral solutions against MPXV in the future