Figure 1.
(A) The secondary structure of MTx (PDB ID 1TXM [32]). α-Helix is shown in purple and β-sheets in yellow. The side chains of four key residues are highlighted. (B) Sequence alignment of the pore domains of Kv1.1, Kv1.2 and Kv1.3. Key different residues are highlighted in green. The P-loop turret and selectivity filter regions are indicated with horizontal bars. Numbering is that of Kv1.2. (C) Pore domain of Kv1.2 (PDB ID 3LUT [30]) viewed perpendicular to the channel axis. Two channel subunits are shown. The side chain of Asp355 and the backbone carbonyl groups of Thr373 and Asp379 are highlighted. Green spheres represent the two K+ ions in the selectivity filter. The two water molecules in the selectivity filter are also shown.
Figure 2.
In (A), two key residue pairs Lys23-Tyr377 and Arg14-Asp355 are highlighted. Two channel subunits are shown for clarity. (B) The MTx-Kv1.2 complex rotated by approximately 90° clockwise from that of (A). The third key residue pair Lys7-Asp363 is highlighted in (B).
Figure 3.
Time evolution of the salt bridge lengths.
The lengths of the salt bridges Arg14-Asp355 and Lys7-Asp363 formed in the MTx-Kv1.2 complexes as a function of the simulation time over the last 15 ns.
Figure 4.
In (A), two key residue pairs Lys23-Tyr377 and S6-Asp379 are highlighted. In (B), residue pairs Lys23-Tyr377 and Lys30-Asp379 are highlighted.
Figure 5.
The PMF profiles for the unbinding of MTx from Kv1.1, Kv1.2 and Kv1.3.
The reaction coordinate is the distance between the centers of mass of the channel and toxin along the channel axis (z).
Table 1.
The average changes in van der Waals () and electrostatic (
) interaction energies (kcal/mol) between MTx and the surroundings due to the binding of MTx to Kv1.1–Kv1.3 channels.
Figure 6.
The position of MTx (yellow) relative to Kv1.1-Kv1.3 channels.
The key residue 381 is highlighted in red. Green arrows represent the dipole moment of MTx.