Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor of Yersinia pestis

Kuban-Jankowska, Alicja; Sahu, Kamlesh K; Niedzialkowski, Pawel; Gorska, Magdalena; Tuszynski, Jack A; Ossowski, Tadeusz; Wozniak, Michal

Top scoring poses from docking that interacted with Cys403 were retained for molecular dynamics simulations using amber12. We allowed Leap module of Amber [29] to add missing hydrogen atoms and heavy atoms using the Amber force field (ff10) parameters [30] . To neutralize the charge of the system, we added sodium/chloride ions. The model was immersed in a truncated cubical shell of TIP3P water [31] . A time step of 2 fs and a direct-space non-bonded cutoff of 10 Ã… were used. After the protein preparation, all systems were minimized to remove the steric clashes that occurred. The systems were then gradually heated from 10 to 300 K over a period of 50 ps and then maintained in the isothermal-isobaric ensemble (NPT) at a target temperature of 300 K and a target pressure of 1 bar using a Langevin thermostat [32, 33] and a Berendsen barostat with a collision frequency of 2 ps and a pressure relaxation time of 1 ps, respectively. We constrained hydrogen bonds using the SHAKE algorithm [34] . We have used the velocity-Verlet algorithm (default algorithm for the Amber MD package) for MD simulations. Particle mesh Ewald (PME) procedure was used to treat long-range electrostatic interactions using default parameters [35] . After bringing the systems at our suitable temperature and pressure of 300 K and 1 bar, respectively and equilibrating the system for 500 ps, the production run was continued for 20 ns in the isothermal-isobaric ensemble at the target temperature of 300 K and target pressure of 1 bar using the same Langevin thermostat and Berendsen barostat. The structures in the trajectories were collected at 10 ps intervals. The analysis of trajectories was performed with the Ptraj module of Amber.