ABSTRACT
COVID-19 has been threatening human health since the late 2019, and has a significant impact on human health and economy. Understanding SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronavirus-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found that SARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). Energy pH-dependence calculations revealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Three independent 100 ns molecular dynamics (MD) simulations were performed using NAMD to investigate the hydrogen bonds between S proteins RBD and hACE2 RBD. From MD simulations, we found that SARS-CoV-2 forms 19 pairs (average of three simulations) of hydrogen bonds with high occupancy (>50%) to hACE2, compared to 16 pairs between SARS-CoV and hACE2. Additionally, SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors. We also labelled key residues involved in forming the top five hydrogen bonds that were found in all three independent 100 ns simulations. This identification is important to potential drug designs for COVID-19 treatments. Our work will shed the light on current and future coronavirus-caused diseases.
ABSTRACT
COVID-19 has been threatening human health since the late 2019, which has significant impact on human health and economy. Understanding the SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronaviruses-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found thatSARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). The energy pH-dependence calculation srevealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Molecular dynamics simulations were performed using NAMD to investigate the hydrogen bonds between S proteins and hACE2. From the MD simulations it was found that SARS-CoV-2 has four pairsof essential hydrogenbonds (high occupancy, >80%), while SARS-CoV has three pairs, which indicates the SARS-CoV-2 S protein has relatively more robust binding strategy than SARS-CoVS protein.Four key residues forming essential hydrogen bonds from SARS-CoV-2 are identified, which are potential drug targets for COVID-19 treatments. The findings in this study shed lights on the current and future treatments for COVID-19 and other coronaviruses-caused diseases.