Umbrella sampling in combination with a polarizable QM/MM model have been used to study the role of electrostatics and polarization in the translocation and selectivity properties of two K+ channels, KcsA and KirBac, with ions traversing the channel according to an ion−water−ion mechanism. Analysis of electrostatic interaction energies shows an increased electrostatic gradient within the KirBac channel relative to KcsA. Quantitative measurements of polarization effects induced by ions and water molecules in the channel suggest a decreased interaction with K+ and Rb+ close the S2 binding site. This effect cannot be explained solely by the geometry of the polarizable region, or by conformational changes in the filter, but appears to be due to the polarization of the valine residue of the TVGYG selectivity filter motif. We observe that the presence of an ion in the S2 site, and the absence of an ion at the S3 site, where there is a water molecule instead, depolarizes valine and, hence, decreases the interaction energy between that residue and the ion in S2. Our results suggest that the incorporation of polarization effects can make an observable difference to the potential experienced by an ion in the channel.
- KCSA POTASSIUM CHANNEL, MOLECULAR-DYNAMICS SIMULATIONS, QUANTUM-MECHANICAL CALCULATIONS, ION CONDUCTION, CONFORMATIONAL-CHANGES, COORDINATION NUMBERS, POTENTIAL FUNCTIONS, ATOMIC CHARGES, PERMEATION, FILTER