Molecular dynamics simulations of the gramicidin A-dimyristoylphosphatidylcholine system with an ion in the channel pore region

To investigate the process of ion permeation in an ion channel systematical ly, we performed molecular dynamics (MD) simulations on a gramicidin A (GA) -phospholipid model system with an ion in the channel pore region. Each of the three types of ions (Ca2+, Na+, Cl-) was placed at five different posit ions along the channel axis by replacing a water molecule. MD simulations w ere performed on each system at constant pressure and constant temperature. The MD trajectories showed that the Ca2+ and Na+ ions could stably fluctua te in the pore region, but the Cl- ion was pushed out because of the unfavo rable interaction with the channel. This result is consistent with experime ntal data. It was also found that the conformation of the GA channel underw ent a significant change due to the presence of the ion, and the two ends o f the GA monomer were more flexible than its middle region. In particular, the dramatic change of local pore radius near the ion indicated this kind o f deformation. The strong interaction between the ion and carbonyl oxygen a toms of GA was the major contributor to this change. Furthermore, it was fo und that the ethanolamine group of the GA molecule was the most flexible gr oup in the GA channel and often observed to block the entrance of GA. These results imply that the deformation of channel structure plays a very impor tant factor in ion permeation, and the ethanolamine group may play a key ro le in regulating ion entry into the pore. In conclusion, our results indica te that the ion has a dominant influence on the structure of the GA channel and that the flexibility of the ion channel is a crucial factor in the ion permeation process.