Paper Citing NAMD - Abstract
Khalili-Araghi, Fatemeh; Jogini, Vishwanath; Yarov-Yarovoy, Vladimir; Tajkhorshid, Emad; Roux, Benoit; Schulten, Klaus
Calculation of the Gating Charge for the Kv1.2 Voltage-Activated Potassium Channel
BIOPHYSICAL JOURNAL, 98:2189-2198, MAY 19 2010
The atomic models of the Kv1.2 potassium channel in the active and resting state, originally presented elsewhere, are here refined using molecular dynamics simulations in an explicit membrane-solvent environment. With a minor adjustment of the orientation of the first arginine along the S4 segment, the total gating charge of the channel determined from >0.5 mu s of molecular dynamics simulation is similar to 12-12.7 e, in good accord with experimental estimates for the Shaker potassium channel, indicating that the final models offer a realistic depiction of voltage-gating. In the resting state of Kv1.2, the S4 segment in the voltage-sensing domain (VSD) spontaneously converts into a 31,3 helix over a stretch of 10 residues. The 3(10) helical conformation orients the gating arginines on S4 toward a water-filled crevice within the VSD and allows salt-bridge interactions with negatively charged residues along S2 and S3. Free energy calculations of the fractional transmembrane potential, acting upon key charged residues of the VSD, reveals that the applied field varies rapidly over a narrow region of 10-15 angstrom corresponding to the outer leaflet of the bilayer. The focused field allows the transfer of a large gating charge without translocation of S4 across the membrane.
