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

Furthermore, molecular dynamics simulations were performed for the inhibitor-complexed system HA1-Neo6 and the inhibitoruncomplexed system HA1, respectively. The root mean square deviation (RMSD) from initial conformation is a central criterion used to evaluate the difference of the protein system. The stability of a simulation system was evaluated based on its RMSD. The RMSD values for both Neo6-HA1 (green curve) and HA1 (red curve) versus the simulation time were illustrated in Fig. 5A , in which the RMSD for Neo6-HA1 system is a little smaller than that of HA1 system, indicating that the flexibility of HA1 was decreased after the Neo6 binding to HA1. In order to investigate the motions about the important residues interacted with the inhibitor in the binding site defined as loops (Loop1-Loop4) in Fig. 1 , the root mean square fluctuations (RMSF) for all the sidechain atoms of protein were calculated, as shown in Fig. 5B . The curves of RMSF associated with Loop1, Loop2, Loop3, and Loop4 are colored orange, light blue, dark blue, and maroon, respectively. It can be clearly seen from Fig. 5 that the fluctuating magnitudes of the four loops in HA1 are much larger than those in Neo6-HA1, clearly indicating that the receptor HA1 is more stable after binding with the ligand Neo6. The RMSD for all backbone atoms of the Neo6-HA1 system (green) and the HA1 system (red). (B) The RMSF for side-chain atoms of the Neo6-HA1 system (green) and the HA1 system (red). The curves associated with Loop1, Loop2, Loop3, and Loop4 are colored orange, light blue, dark blue, and maroon, respectively. doi:10.1371/journal.pone.0028111.g005 Accordingly, among the series of Neo compound candidates, Neo6 is anticipated to be a promising drug candidate for further experimental investigation to develop new and effective drug against influenza viruses.