Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands

Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K + over Na + by more than a thousand-fold. This selectivity arises because the transfer of the K + ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K + ion and carbonyl groups lining the rigid and narrow pore 1 . But proteins are relatively flexible structures 2 , 3 that undergo rapid thermal atomic fluctuations larger than the small difference in ionic radius between K + and Na + . Here we present molecular dynamics simulations for the potassium channel KcsA, which show that the carbonyl groups coordinating the ion in the narrow pore are indeed very dynamic (‘liquid-like’) and that their intrinsic electrostatic properties control ion selectivity. This finding highlights the importance of the classical concept of field strength 4 . Selectivity for K + is seen to emerge as a robust feature of a flexible fluctuating pore lined by carbonyl groups.