107 / 119
Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
102
36-POS
Board 36
Quantum Calculations on a Voltage Sensing Domain of Kv1.2: H
+
Transfer and Gating
Current
Alisher M. Kariev
1
,
Michael E. Green
1
.
1
n/a, New York, USA,
2
City College of Cuny, New York, NY, USA.
Quantum calculations on a 904 atom segment of the voltage sensing domain (VSD) of Kv1.2,
with 24 water molecules added, starting from X-ray coordinates (pdb:3Lut), show how protons
may traverse the section, and become the gating current. With the S4 segment free to move, and
a -107 Vm-1 field applied (equivalent membrane potential: V≈-70 mV), the segment backbone
moves <2.5 Å, and not in the intracellular direction, as required in standard models of gating.
Second, we have optimized (energy minimized) structures with protons in several positions,
testing whether salt bridges present in the VSD may be neutralized; earlier work has shown that
salt bridges in the absence of water do not ionize (Liao and Green, CompTheoChem, 2011).
Here, energy is lower for the unionized form in certain cases with V<0 (closed channel), but not
with V≥0 (open channel). Specific cases which would add to gating current, including a transfer
of a proton from a tyrosine (Y266) to the pre-guanidinium nitrogen of a neighboring S4 arginine,
are shown, with accompanying energy for the proton in each position. For the lowest energy
states, closed (-70mV) the charges on Y266, R300, and E183 are 0,0,0; at 0 mV (open), -,+,0,
respectively (nominal charges—actual charges are not integral). Open energy is ≈15kBT higher.
The proton appears able to move to E183 by way of R300, providing in total about 0.6 charges of
gating current. Optimization to get structure used HF/6-31G*, followed by more accurate energy
calculation at B3LYP/6-31G**, plus NBO for atomic charges. Additional cases have been
calculated, including some with V=+70mV; the open and closed cases shown above have the
lowest energy of a substantial set of plausible states.