Molecular dynamics simulations of calcium binding in gramicidin A

An important issue in molecular dynamics (MD) simulations of biomolecules is whether membrane proteins can be described using nonpolarizable force fields. To shed further light into this question, we study calcium ion binding and blocking of the gramicidin A channel which has not been investigated in MD simulations before. Potential of mean force calculations for calcium and potassium ions using a nonpolarizable force field reveal that calcium binding to the channel is much weaker compared to potassium, and hence calcium block of potassium current cannot be described. Inclusion of polarization interaction in force fields may help to rectify this problem.

A calcium ion (blue) near the binding site of the gramicidin A channel (green helix). The ion is mainly hydrated by the water molecules (red and white spheres) but sometimes makes contact with the Leu14 oxygen (red sphere near the helix) as shown in the figure.