Structure and dynamics of membrane protein in SARS-CoV-2

Abstract

SARS-CoV-2 membrane (M) protein performs a variety of critical functions in virus infection cycle. However, the expression and purification of membrane protein structure is difficult despite tremendous progress. In this study, the 3 D structure is modeled followed by intensive validation and molecular dynamics simulation. The lack of suitable homologous templates (>30% sequence identities) leads us to construct the membrane protein models using template-free modeling (de novo or ab initio) approach with Robetta and trRosetta servers. Comparing with other model structures, it is evident that trRosetta (TM-score: 0.64; TM region RMSD: 2 Å) can provide the best model than Robetta (TM-score: 0.61; TM region RMSD: 3.3 Å) and I-TASSER (TM-score: 0.45; TM region RMSD: 6.5 Å). 100 ns molecular dynamics simulations are performed on the model structures by incorporating membrane environment. Moreover, secondary structure elements and principal component analysis (PCA) have also been performed on MD simulation data. Finally, trRosetta model is utilized for interpretation and visualization of interacting residues during protein-protein interactions. The common interacting residues including Phe103, Arg107, Met109, Trp110, Arg131, and Glu135 in the C-terminal domain of M protein are identified in membrane-spike and membrane-nucleocapsid protein complexes. The active site residues are also predicted for potential drug and peptide binding. Overall, this study might be helpful to design drugs and peptides against the modeled membrane protein of SARS-CoV-2 to accelerate further investigation.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• SARS-CoV-2 membrane protein
• modeling approach
• template-free modeling
• model validation
• molecular dynamics
• principal component analysis
• protein-protein interactions

Acknowledgements

We are grateful to our donors (http://grc-bd.org/donate/) who supported to build a computational platform. The authors like to acknowledge The World Academy of Science (TWAS) to purchase the High-Performance Computers for molecular dynamics simulation. We also like to give special thanks to Mst. Noorjahan Begum, Research Investigator, Virology Laboratory, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh; Md. Waseque Mia, Assistant Professor, Dept. of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet-3114, Bangladesh; Md Nayeem Hossain, Sayeda Samina Ahmed, Rajib Islam, Md. Rimon Parvez, Division of Infectious Diseases and Division of Computer Aided Drug Design, The Red-Green Research Centre, Dhaka, Bangladesh for their cordial support and valuable suggestions.

Disclosure statement

The authors declare no competing financial interest.