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

For each system, all-atom MD simulations were performed for an N, P, T ensemble in explicit solvent (water and ions) using NAMD 2.13 (Phillips et al. 2005 ) package with CHARMM36 (Best et al. 2012 ) force field. MD Simulations were performed at 310 K temperature and 1 bar pressure. Periodic boundary conditions were applied. Langevin dynamics was used to control the system temperature and pressure. All atoms were coupled to the heat bath. A time step of 2 fs was used. Two minimization-equilibration cycles were applied: All steps were applied under N, P, T conditions to relax water and find a local minimum of the whole system energy (Phillips et al. 2003) . The energy of the initial system was first minimized for 10000 steps. Water was then equilibrated by keeping the protein fixed for 2 ns. Then, the system was minimized for 10000 steps. After the second minimization step, a harmonic constraint, which has 1 −1 Å −2 spring constant, was applied to each Cα of the protein for 20 ns. At the third equilibration step, protein was released and the system was equilibrated for 5 ns. This equilibrium step is expected to be sufficient simulate the structural differences due to the radically different thermodynamic conditions of crystallization solutions and conventional MD simulations (Pullara et al. 2019 ). Finally, production MD simulations were performed. Atomic coordinates of all atoms, pressures and the energies were recorded every 10 ps. Two sets of MD simulations were performed for each of the closed and open states of the S protein. A total length of 800 ns of MD simulations starting from the crystal structures were performed. Table I presents the complete list and length of each MD simulations performed in the present study.