Targeted molecular dynamics of an open-state KcsA channel
Pore opening of KcsA channel is studied using targeted molecular dynamics simulations. Conformational changes of the protein are determined, starting from the crystallized refined 2.0 Å structure (pdb 1K4C) determined in x-ray experiments and arriving to the open-state structure constructed on the basis of electron paramagnetic resonance spectroscopic data (pdb 1JQ1). Our results corroborate the essential role played by the terminal residues located on the transmembrane helices M2 which were not taken into account at that time. The aperture mechanism of the channel appears to be ziplike. A small constraint ( ≈ 5×10−2 kcal mol−1 Å−2 per Cα) applied to the terminal residues located on the intracellular side is sufficient to initialize the pore opening at the innermost part of the gate, but additional constraint must be applied to definitely complete the pore aperture. The open structure is proved to be a metastable state since releasing the constraint leads to another relaxed open conformation which seems to reach stability.