Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

Li, Xiao-Bo; Wang, Shu-Qing; Xu, Wei-Ren; Wang, Run-Ling; Chou, Kuo-Chen

In order to examine whether the designed inhibitor remains bound in the presence of explicit solvent from a dynamic point of view, the molecular dynamic simulation was performed with GROMACS 96-53a6 force fields [55] with the periodic boundary conditions (PBC) by using GROMACS 4.0 package for Linux. The topology files and charges for the ligand atoms were generated by the Dundee PRODRG2.5 Server (beta) [56] . Before starting the simulations, all the models were solvated with the explicit simple point charge (SPC) water in a cubic box. The models were covered with a water shell of 1.0 nm from the surface of the protein. The system was neutralized with six chlorine ions to replace the six SPC water molecules. Subsequently, the energy minimization was performed for the system concerned by using the steepest descent until touching a tolerance of 100kJ/mol. And then, the 10 ns MD simulations were carried out with a time step of 1 fs; the corresponding coordinates were stored every 100 fs. The PME algorithm was used to calculate the electrostatic interactions. All simulations were run under the periodic boundary condition with NVT ensemble by using Berensen's coupling algorithm for keeping the temperature at 310 K and pressure at 1atm. All bonds were constrained by using the LINCS algorithm. The GROMACS 4.0 package was utilized to analyze the results.