MD Simulations Of The Influences Of An External Force On The Water Transportation Behavior Through A Transmembrane Peptide Nanotube

Cyclic peptide nanotubes (cyclic PNTs) are one class of synthetic nanochannels, widely used in the simulations of biological water channels. Water transportation characteristics of channel proteins may change under some external stimuli. In this work, the mechanism how an external force influences PNT channel structure and water transportation characteristics have been explored in detail.Steered molecular dynamics (SMD) simulations with constant velocity and constant force schemes have been performed to study the gating mechanism of water permeation across a transmembrane peptide nanotube of8×cyclo-(WL)4/POPE under an external force (F=0-2.0nN) exerted on the C5atom of P4subunit. The results show that the diameter deformation quantity (δC3-C7) of P4subunit increases with the augment of force. The P3and P5subunits on both sides of P4subunit also have certain deformation, due to the H-bonded interactions between these adjacent peptide subunits. The P4subunit was pulled into an oval with a size of13.3A×5.6A under an external force of2.0nN. The channel was completely closed then. The structural deformation of the nanotube framework directly leads to a change of water-chain structure, causing water molecular configuration in the zones between P3and P5subunits to change somewhat. No obvious change was observed within0.8nN of external force. If the external force increases to1.6nN, no water molecule could exist at the position of the force exertion at z=2.4A. However, there was still a small amount of water flow in the channel then. The computations of the free energies [G(N)] of different water molecular occupancies (N) under individual external forces indicate that the optimal number of water molecules changes little and almost maintains22within0.8nN of external force. But it would reduce when the external force further increase, becoming18when the external force increases to1.6nN and maintaining the number under an even larger force. The H-bonded water-chain would be gradually destroyed with the force increasing. The numbers of the H-bonded on both sides of P4subunit maintain8within0.8nN and0.9nN of external forces, respectively. Only two and four H-bonds between P4and P3, P5subunits were reserved under an external force of2.0nN. Water molecular dipole orientations in the region between P3and P4subunits tend to be more directed, due to the simultaneous formation of H-bonds between the two H atoms of a water molecule and carbonyl oxygen atoms of the PNT framework. Water flow in the nanotube maintains six water molecules when the external force is less than0.8nN, and decreases to zero under an external force of2.0nN, indicating that the cyclic PNT is completely closed. These findings would likely cast light on the study of the response of water permeation through a nanotube to an external force.