Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations

Mert Gur; Elhan Taka; Sema Zeynep Yilmaz; Ceren Kilinc; Umut Aktas; Mert Golcuk

Starting The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.17.047324 doi: bioRxiv preprint motion. Since there is no noticeable structural difference between the RBD structures, the difference in the RBD mobility in the open and closed state is expected to be caused by differences in interdomain interactions of RBD. To this aim, interdomain salt bridges of RBD with the remaining parts of protein were investigated in the closed and open states. Based the closed state crystal structure, RBD forms the following three interdomain salt bridges with residues of neighboring protomer; K378-E988 and K386-D985 with domain S2, and E516-K202 with NTD. Significantly, upon performing MD simulations in the closed state the following additional interdomain salt bridges of RBD formed with its neighboring protomers: R408-D405 with RBD, K458-D985 with S2 domain, and K462-D198 with NTD (Fig. 2) . The distribution of the distances between the basic nitrogens and acidic oxygens of these 6 interdomain salt bridges of RBD are shown in Fig. 4 . As can be seen the most prevalent salt bridge observed in MD simulations was R408-D405. Compared to its down position, RBD made significantly less interdomain salt bridges in its up position. Although there were no interdomains salt bridges present for RBD of protomer B in its up conformation in the open state crystal structure, MD simulations demonstrated the formation of the following interdomain salt bridges of RBD of protomer B with its neighbors: D428-R403 with RBD of protomer A, and R357-E169 and R466-E132 with NTD of protomer C. The distributions of the distances between the basic nitrogens and acidic oxygens of these 3 salt bridges are depicted in Fig. 4(b) .