Mechanism of Ion Transport Across Membranes Assisted by Molecular Shuttles

Abstract

The mechanism of K+ transmembrane transport assisted by a rotaxane-based molecular shuttle was studied by advanced enhanced sampling molecular dynamics simulations. The rotaxane consisted of an amphiphilic axel, a large crown ether wheel sliding on the axle, and a linked small crown ether carrier. There were three positively charged binding sites on the axel. By calculating the free-energy change of the shuttle process, the effects of solvents(chloroform, acetonitrile, water, and chloroform-acetonitrile) and the middle binding site on the shuttle movement of the rotaxane were explored. Furthermore, the important role of the middle bin- ding site in transmembrane ion transport across cell membranes(using water-chloroform-water to simulate) was analyzed. The results indicate that changing the solvent does not alter the movement mode of the rotaxane (without K+), but as the polarity of the solvent increases, the free energy barrier against the shuttle significantly decreases. In the chloroform-acetonitrile mixed solvent, the protonation state of the middle binding site does not affect the free energy barrier against shuttling of the rotaxane(without K+). However, in the environment of the simulated cell membrane, compared with deprotonation, the protonation of this binding site significantly decreases the free energy barrier of shuttling and facilitates the transport of the K+ across the membrane, indicating that the protonation of the middle binding site is paramount importance for ion translocation. Further analysis shows that the cooperation between the shuttling movement of the large ring and the swinging movement of the small ring constitutes another key factor in accelerating transmembrane ion transport.