The Molecular Basis of the Effect of Temperature on the Structure and Function of SARS-CoV-2 Spike Protein

Abstract

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production. Several researchers studied the nature of this protein under various environmental conditions. In this work, we applied molecular modeling and extensive molecular dynamics simulation approaches at 0°C (273.15 K), 20°C (293.15 K), 40°C (313.15 K), and 60°C (333.15 K) to study the detailed conformational alterations in the SARS-CoV-2 S protein. Our aim is to understand the influence of temperatures on the structure, function, and dynamics of the S protein of SARS-CoV-2. The structural deviations, and atomic and residual fluctuations were least at low (0°C) and high (60°C) temperature. Even the internal residues of the SARS-CoV-2 S protein are not accessible to solvent at high temperature. Furthermore, there was no unfolding of SARS-CoV-2 spike S reported at higher temperature. The most stable conformations of the SARS-CoV-2 S protein were reported at 20°C, but the free energy minimum region of the SARS-CoV-2 S protein was sharper at 40°C than other temperatures. Our findings revealed that higher temperatures have little or no influence on the stability and folding of the SARS-CoV-2 S protein.

Modeling of the thermal properties of SARS-CoV-2 S-protein

“…The FEL provides insight into the S-protein conformational changes and the thermodynamics properties of the S-protein folding process. The FEL, a measurement calculated for the protein stability level, uses the deep valley to represent the lowest energy stable states and the boundaries between deep valleys to represent the intermediate conformations ( Hoang et al, 2004 ; Khan et al, 2020 ; Khan et al, 2022 ).…”

“…MD modeling has been used to investigate the binding characteristics of SARS-CoV-2; however, long-timescale MD simulations to study the temperature influence on the S-protein’s closed state conformation are uncommon. The recent work focuses on the open state of S-protein and reveals the S-protein structure details effect by 0°C–60°C in 100 ns ( Khan et al, 2022 ). Therefore, our work with longer simulations (reach 3 μs) and a wider range of temperatures (3°C–95°C) exposes the closed state of S-protein 6VXX.PDB ( Walls et al, 2020 ) trajectory and multi-granularity analysis, providing new insights into the RBD closed state influenced by temperature.…”