Potassium channels are a diverse family of integral membrane proteins through which K+ can pass selectively. There is ongoing debate about the nature of conformational changes associated with the opening/closing and conductive/nonconductive states of potassium channels. The channels partly exert their function by varying their conductance through a mechanism known as C-type inactivation. Shortly after the activation of K+ channels, their selectivity filter stops conducting ions at a rate that depends on various stimuli. The molecular mechanism of C-type inactivation has not been fully understood yet. However, the X-ray structure of the KcsA channel obtained in the presence of low K+ concentration is thought to be representative of a K+ channel in the C-type inactivated state. Here, extensive, fully atomistic molecular dynamics and free-energy simulations of the low-K+ KcsA structure in an explicit lipid bilayer are performed to evaluate the stability of this structure and the selectivity of its binding sites. We find that the low-K+ KcsA structure is stable on the timescale of the molecular dynamics simulations performed, and that ions preferably remain in S1 and S4. In the absence of ions, the selectivity filter evolves toward an asymmetric architecture, as already observed in other computations of the high-K+ structure of KcsA and KirBac. The low-K+ KcsA structure is not permeable by Na+, K+, or Rb+, and the selectivity of its binding sites is different from that of the high-K+ structure.
- Bacterial Proteins, Models, Chemical, Potassium Channels, Protein Conformation, Protein Stability, Thermodynamics