How Does Temperature Affect the Dynamics of SARS-CoV-2 M Proteins? Insights from Molecular Dynamics Simulations

• Published in: The Journal of membrane biology 2022-06, Vol.255 (2-3), p.341-356
• Main Authors: Rath, Soumya Lipsa, Tripathy, Madhusmita, Mandal, Nabanita
• Format: Article
• Language: English
• Subjects: Agglomeration; Biochemistry; Biochemistry & Molecular Biology; Biomedical and Life Sciences; Cell Biology; COVID-19; Drug development; Glycoproteins; Human Physiology; Humans; Life cycles; Life Sciences; Lipids; Low temperature; M protein; Membrane Lipids; Membrane proteins; Membranes; Molecular dynamics; Molecular Dynamics Simulation; Physiology; Protein interaction; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Simulation; Temperature; Temperature dependence; Temperature effects; Viral diseases; Viruses
• ISSN: 0022-2631; 1432-1424; 1432-1424
• DOI: 10.1007/s00232-022-00244-y

Enveloped viruses, in general, have several transmembrane proteins and glycoproteins, which assist the virus in entry and attachment onto the host cells. These proteins also play a significant role in determining the shape and size of the newly formed virus particles. The lipid membrane and the embedded proteins affect each other in non-trivial ways during the course of the viral life cycle. Unraveling the nature of the protein–protein and protein–lipid interactions, under various environmental and physiological conditions, could therefore prove to be crucial in development of therapeutics. Here, we study the M protein of SARS-CoV-2 to understand the effect of temperature on the properties of the protein-membrane system. The membrane-embedded dimeric M proteins were studied using atomistic and coarse-grained molecular dynamics simulations at temperatures ranging between 10 and 50 °C. While temperature-induced fluctuations are expected to be monotonic, we observe a steady rise in the protein dynamics up to 40 °C, beyond which it surprisingly reverts back to the low-temperature behavior. Detailed investigation reveals disordering of the membrane lipids in the presence of the protein, which induces additional curvature around the transmembrane region. Coarse-grained simulations indicate temperature-dependent aggregation of M protein dimers. Our study clearly indicates that the dynamics of membrane lipids and integral M protein of SARS-CoV-2 enables it to better associate and aggregate only at a certain temperature range (i.e., ~ 30–40 °C). This can have important implications in the protein aggregation and subsequent viral budding/fission processes. Graphical Abstract