Potential Neutralizing Antibodies Discovered for Novel Corona Virus Using Machine Learning

Rishikesh Magar; Prakarsh Yadav; Amir Barati Farimani

To assess the stability of proposed antibody structures, we performed molecular dynamics (MD) simulations of each of antibody structure in a solvated environment 98 . The simulation of solvated antibody was carried out using GROMACS-5.1.4 [99] [100] [101] , and topologies for each antibody were generated according the GROMOS 54a7 102 forcefield. The protein was centered in a box, extending 1 nanometer from surface of the protein. This box was the solvated by the SPC216 model water atoms, pre-equilibrated at 300K. The antibody system in general carried a net positive charge and it was neutralized by the counter ions. Energy minimization was carried out using steepest descent algorithm, while restraining the peptide backbone to remove the steric clashes in atoms and subsequently optimize solvent molecule geometry. The cut-off distance criteria for this minimization were forces less than 100.0 kJ/mol/nm or number of steps exceeding 50,000. This minimized structure was the sent to two rounds of equilibration at 300K. First, an NVT ensemble for 50 picoseconds and a 2-femtosecond time step. Leapfrog dynamics integrator was used with Verlet scheme, neighbor-list was updated every 10 steps. All the ensembles were under Periodic Boundary Conditions and harmonic constraints were applied by the LINCS algorithm 103 ; under this scheme the long-range electrostatic interactions were computed by Particle Mesh Ewald (PME) algorithm 104 . Berendsen thermostat was used for temperature coupling and pressure coupling was done using the Parrinello-. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.14.992156 doi: bioRxiv preprint Rahman barostat 105, 106 . The last round of NPT simulation ensures that the simulated system is at physiological temperature and pressure. The system volume was free to change in the NPT ensemble but in fact did not change significantly during the course of the simulation. Following the rounds of equilibration, production run for the system was carried out in NPT and no constraints for a total of 15 nanoseconds, under identical simulation parameters.