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 Ca(2+) 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 Ca(2+) 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 Ca(2+), 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 Ca(2+) with respect to the pore axis, and provide additional details of ion-protein interactions that govern selectivity.
Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032, India.
Siladitya
S
Padhi
Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032, India.
U Deva
UD
Priyakumar
D002118:Calcium / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D017136:Ion Transport; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D015221:Potassium Channels; D014764:Viral Proteins; D011188:Potassium; D002118:Calcium