Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/078113 doi: bioRxiv preprint The simulation cell is a dodecahedron with a periodicity of 12 Ã… between the protein and the box walls to ensure protein will not interact with its own periodic images. Water molecules using the TIP3P model are used to solvate the MD system. 8 Na + ions were added into the Zika NS2B-NS3pro to make the charge of the respective MD system neutral. The solvated Zika homology NS2B-NS3pro complex was first energy minimized with 1000 steps of steepest descent using GROMACS version 4.5.7 (40) using AMBER all-atom force field (41) . The time step was set as 2 fs. Prior to MD production simulation, two stages of equilibration were done independently for each MD simulation set. First equilibration phase was done in NVT ensemble for 100 ps with the following settings: long-range electrostatic interactions calculated with fast particle-mesh Ewald summation method; a cutoff of 9 Ã… for electrostatic interactions and a cutoff of 14 Ã… for van der Waals interactions; the temperature was kept constant at 300 K with Berendsen's coupling. Second equilibration phase was done in NPT ensemble for 100 ps with the same settings as the first equilibration phase and some additional settings: pressure coupling was held at 1 bar with Parrinello-Rahma coupling; isothermal compressibility was set at 4.5*10 bar. Heavy atoms of proteins were positioncontrained using LINCS algorithm (42) . The MD production simulation was done with the same settings with NPT equilibration without the position-contraints on heavy atoms of protein and temperature coupling was done with Nose-Hoover. author/funder. All rights reserved. No reuse allowed without permission.