Molecular dynamics study of Na+ transportation in a cyclic peptide nanotube and its influences on water behaviors in the tube

Abstract

The dynamics of Na(+) transportation in a transmembrane cyclic peptide nanotube of 8 × (WL)4/POPE has been simulated. The curve of PMF (potential of mean force) for Na(+) moving through the tube, based on ABF (adaptive biasing force) method, indicates that Na(+) possesses lower free energy in an α-plane region than in a mid-plane one. It was found that Na(+) would desorb one or two water molecules in the first solvation shell when entering the tube and later maintain in a solvation state. The average numbers of water molecules around Na(+) are 4.50, 4.09 in the first solvation shell, and 3.10, 4.08 in the second one for Na(+) locating in an α-plane zone and a mid-plane region, respectively. However, water molecules far away from Na(+) location still nearly arrange in a form of 1-2-1-2 file. The dipole orientations of water molecules in the regions of gaps 1 and 7 display "D-defects", resulted from the simultaneous electrostatic potentials generated by Na(+) and the bare carbonyls at the tube mouths. Such "D-defects" accommodate the energetically favorable water orientations thereby.

Transport Behavior of a Single Ca2+, K+, and Na+ in a Water-Filled Transmembrane Cyclic Peptide Nanotube

“…By calculating the PMF profiles of Na + , K + , and Cl − permeating through a CPNT embedded in water on the basis of the umbrella sampling scheme and thermodynamic integration approach, respectively, Choi et al 25 explored in detail the differences between the selectivities of the CPNT for a cation versus an anion, uncovering free energy wells for Na + and K + but barriers for Cl − in the tube. Based on the PMF of Na + moving through an octa-CPNT, our previous work 26 revealed barriers for Na + in midplane regions and wells in α-plane zones. Granja et al 27 studied the transport properties of several electrolyte solutions in self-assembled α,γ-peptide nanotubes and found that the assembled nanotubes were selective for alkaline ions.…”

Applications of cyclic peptide nanotubes (cPNTs)

“…Generally, the determination of the free energy or diffusion coefficient is a conventional approach used to clarify the feasibility of ionic or molecular transport via cPNTs. The transportation of cations, including K + [ 66 , 72 , 75 , 76 ], Na + [ 66 , 72 , 75 – 77 ], Ca 2+ [ 66 ], and [ 67 ], in cPNTs constructed using different types and numbers of peptides have been studied by MD simulations ( Table 3 ). Among these cations, K + and Na + revealed similar low-energy barriers and diffusion coefficients, thus indicating the easy transport of these two ions in cyclo-(D-Ala-Glu-D-Ala-Gln) 2 [ 75 ] and cyclo-(Trp-D-Leu) n=4,5 cPNTs [ 66 , 76 , 77 ].…”

“…The transportation of cations, including K + [ 66 , 72 , 75 , 76 ], Na + [ 66 , 72 , 75 – 77 ], Ca 2+ [ 66 ], and [ 67 ], in cPNTs constructed using different types and numbers of peptides have been studied by MD simulations ( Table 3 ). Among these cations, K + and Na + revealed similar low-energy barriers and diffusion coefficients, thus indicating the easy transport of these two ions in cyclo-(D-Ala-Glu-D-Ala-Gln) 2 [ 75 ] and cyclo-(Trp-D-Leu) n=4,5 cPNTs [ 66 , 76 , 77 ]. By contrast, Ca 2+ was calculated to have a higher energy barrier than K + and Na + ; therefore, it was considered that it did not easily enter cyclo-(Trp-D-Leu) 4 cPNTs but may enter cyclo-(Trp-D-Leu) 5 cPNTs with large radii [ 66 ].…”

Molecular dynamics studies on the influences of a gradient electric field on the water chain in a peptide nanotube

“…Actually, cyclic peptide nanotubes (PNTs) have better biocompatibility and have been widely used to simulate ion and water channels [31][32][33][34][35][36]. As reported [31,32], water molecules in a cyclic octa-PNT under a zero field arrange themselves mainly in a 1-2-1-2 file.…”