MD Studies On The Tilt Behavior Of A Cyclic Peptide Nanotube And Influences On The Transport Characteristics Of Channel Water

MD simulations have been carried out to study the tilt behaviors of the8×(WL)4-CPNT embedded in the POPE bilayer in a water environment and under an anhydrous condition, respectively. Besides, the influences of the CPNT tilt on the transport characteristics of channel water have been explored.Both 100-ns simulation trajectories and PMF profiles indicate that the presence of water may exacerbate the tilt of the CPNT. The CPNT tilts approximately 8-22° in a water environment, while 3-9° under an anhydrous condition. A water environment may increase the activities of the hydrophilic headgroups of lipids, and the hydrophobic tails may become more active under an anhydrous condition. The active phospholipid heads or tails both easily probe into the mouth of the CPNT, leading to serious H-bond breakages in end-gaps. Under an anhydrous condition, the ellipticities of the end-CPs may significantly decrease, even as low as 0.4-0.6. Nevertheless,water molecules play important roles in maintaining the roundnesses of the end-CPs and the integrity of the whole CPNT by forming water bridges in the end-gaps. The orientations of the backbone carbonyls of the end-CPs are more easily affected and flexible than those of the mid-CPs. The orientations of the Trp residues are almost independent of the presence of water and may visit one and five major rotamer states for the Trp residues on the mid-CPs and end-CPs, respectively. Cation-π interactions between the indole rings of Trp residues and the headgroups of lipids are the major factor causing the CPNT tilt under an anhydrous condition, while H-bonded interactions between water molecules and the indole rings are primary in a water environment.Averagely, one more channel water molecules may occur in the CPNT with the intensifying of the CPNT tilt angle from 15° to 20°. The newly-added moleculemainly occur in α-plane zones. The dipole orientations of channel water molecules except those in gap 7 are gradually oriented and eventually only take "+dipole" states under 20° of the CPNT tilt, while H-bond defects become especially noticeable in gap7. Electrostatic interactions between channel water and the backbone of the CPNT contribute most to such dipole orientations. The average residence time gradually increases with the intensifying of the CPNT tilt.