AUTHOR=Khan Faez Iqbal , Lobb Kevin A. , Lai Dakun TITLE=The Molecular Basis of the Effect of Temperature on the Structure and Function of SARS-CoV-2 Spike Protein JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.794960 DOI=10.3389/fmolb.2022.794960 ISSN=2296-889X ABSTRACT=The remarkable rise of the current COVID-19 pandemic to every part of the globe has lifted the key concerns for the current public health care 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 simulations approaches at 0℃ (273.15K), 20℃ (293.15K), 40℃ (313.15K), and 60℃ (333.15K) to study the detailed conformational alterations in 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, atomic and residual fluctuations were least at low (0℃) and high (60℃) temperature. Even the internal residues of SARS-CoV-2 S protein are not accessible to solvent at high temperature. Further, there was no unfolding of SARS-CoV-2 spike S reported at higher temperature. The most stable conformations of SARS-CoV-2 S protein was reported at 20℃, but the free energy minimum region of SARS-CoV-2 S protein was sharper at 40℃ than other temperatures. Our findings revealed that higher temperatures have little or no influence on the stability and folding of SARS-CoV-2 S protein.