Stability profile analysis. Root mean square deviation (RMSD) and total energy results from MD are summarized in Figure 5 and provide information on N1-ligand complex and ligand stability. During the 20 ns simulation process, the RMSDs of the four complexes ranged between 1.4-1.7 Å . Xylopine_2 stabilized after 15 ns, and the total energy of the complex equilibrated at 219,000 kcal/mol. The ligand RMSD of Rosmaricine_14 remained stable throughout the simulation, and no evident changes in total energy were observed after 17 ns. The RMSD and total energy of Rosmaricine_15 stabilized after 13 ns. Fluctuations in ligand RMSD was observed in TamifluH for the first 5 ns, but no changes were observed in ligand RMSD and total energy from 5 ns until the end of MD. The larger ligand RMSD fluctuations and higher total energy observed for Xylopine_2 may be attributed to its spatial structure and docking characteristics. Xylopine_2 consists of a bulky xylopine and a 2-aminopyridinium residue linked through 1 in a way similar to that of cis conformations ( Figure 6 ). It is well established that cisconformations are less stable than their transcounterparts, and thus may explain the higher total energy levels for Xylopine_2. In addition, Xylopine_2 binds to N1 though the aminopyridinium residue, allowing the xylopine structure more freedom to rotate and thereby increasing ligand RMSDs and total energy levels.