Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein

Cecylia S. Lupala; Xuanxuan Li; Jian Lei; Hong Chen; Jianxun Qi; Haiguang Liu; Xiao-dong Su

The human ACE2 mutants in complex with CoV2-RBD were constructed as described previously. Each mutant complex model was simulated in two independent trajectories. Furthermore, as the crystal structure of the CoV2-RBD/ACE2 complex became available, two additional simulations were carried out using the crystal structure as the starting model to cross-validate the simulation results based on the homology model. Each trajectory was propagated to 500 ns by following the same protocol as the wild type CoV2-RBD/ACE2 complex simulations. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.005561 doi: bioRxiv preprint Analyses were carried out with tools in GROMACS (rmsd, rmsf, energy, and pairdist) to examine the system properties, including the overall stability, local residue and general structure fluctuations through the simulations. The g_mmpbsa program 22 was applied to extract the molecular mechanics energy E MM (Lennard Jones and electrostatic interactions) between ACE2 and the RBD of spike proteins. VMD and Chimera were applied to analyze the hydrogen bonds, molecular binding interface, water distributions, visualization, and rending model images 23, 24 .