Ion Hydration Dynamics in Conjunction with a Hydrophobic Gating Mechanism Regulates Ion Permeation in p7 Viroporin from Hepatitis C Virus

The selectivity of the p7 channel from hepatitis C virus (HCV) toward K+ over Ca2+ has made the channel an intriguing system for investigating ion permeation. The present study employs umbrella sampling free energy calculations to investigate the atomistic details of cation conduction through the channel. The free energy profiles suggest that the energy barrier for Ca2+ conduction is higher than that for K+ conduction by about 4.5 kcal/mol, thus explaining the selectivity exhibited by the channel toward K+. A hydrophobic stretch in the channel is proposed to be the primary factor that discriminates K+ from Ca2+, and the ion solvation dynamics in this stretch reveals interesting insights into the atomistic mechanisms involved. Two-dimensional free energy landscapes for the ion permeation reveal differences in the lateral motions of K+ and Ca2+ with respect to the pore axis, and provide selectivity. additional details of ion protein interactions that govern selectivity.