Exploring the Dynamic Behaviors and Transport Properties of Gas Molecules in a Transmembrane Cyclic Peptide Nanotube

Abstract

The dynamic behaviors and transport properties of O2, CO2, and NH3 molecules through a transmembrane cyclic peptide nanotube (CPNT) of 8×cyclo-(WL)4/POPE have been investigated by steered molecular dynamics (SMD) simulations and adaptive biasing force (ABF) samplings. Different external forces are needed for three gas molecules to enter the channel. The periodic change of the pulling force curve for a gas traveling through the channel mainly arises from the regular and periodic arrangement of the composed CP subunits of the CPNT. Radial distribution functions (RDFs) between gas and water disclose the density decrease of channel water, which strongly aggravates the discontinuity of H-bond formation between a gas molecule and the neighboring water. Compared to hardly any H-bond formation between CO2 (or O2) and the framework of the CPNT, NH3 can form abundant H-bonds with the carbonyl/amide groups of the CPNT, leading to a fierce competition to NH3-water H-bonded interactions. In addition to direct H-bonded interactions, all three gases can form water bridges with the tube. The potential profile of mean force coincides with the occurring probability of a gas molecule along the tube axis. The energy barriers at two mouths of the CPNT elucidate the phenomenon that CO2 and O2 are thoroughly confined in the narrow lumen while NH3 can easily go outside the tube. Intermolecular interactions of each gas with channel water and the CPNT framework and the formation of H-bonds and water bridges illuminate the different gas translocation behaviors. The results uncover interesting and comprehensive mechanisms underlying the permeation characteristics of three gas molecules traveling through a transmembrane CPNT.

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study

“…Cyclic peptide nanotubes (CPNs), which are a family of synthetic ion channels, involve the formation of tubular structures through intermolecular hydrogen bonding between adjacent cyclic peptide rings composed of alternating d - and l -type amino acid residues. − The diameter of CPNs can be modulated by altering the number of amino acid residues that comprise a cyclic peptide ring, and as a result, CPNs with larger diameters can translocate hydrophilic small molecules or molecular ions across cell membranes due to the hydrophilic nature of the interior of CPNs. Unlike natural channel proteins that selectively and actively permeate ions or small biomoles across cell membranes, CPNs passively transport such ions or molecules due to lack of active functionality in their simple tubular strucure and thus have limitations in the applications.…”

Probing the Role of Imidazopyridine and Imidazophosphorine Scaffolds To Design Novel Proton Pump Inhibitor for H+,K+-ATPase: A DFT Study

“…For the van der Waals (vdW) interactions, smoothing function was employed at a distance of 15 Å and nonbonded interactions list was updated every 20 time steps for pairs within a distance cutoff of 15 Å. After performing all of those equilibration steps, a steered molecular dynamics simulation was carried out for 5 ns, to mimic the transport process of a guest molecule through a nanochannel . We have applied a harmonic force constant of 1586.747 kJ/(mol nm 2 ) to the center of mass (COM) of the ligands with a pulled velocity of 0.0005 nm/ps.…”

“…After performing all of those equilibration steps, a steered molecular dynamics simulation was carried out for 5 ns, to mimic the transport process of a guest molecule through a nanochannel. 74 We have applied a harmonic force constant of 1586.747 kJ/ (mol nm 2 ) to the center of mass (COM) of the ligands with a pulled velocity of 0.0005 nm/ps.…”

Molecular Dynamics Simulations on the Behaviors of Hydrophilic/Hydrophobic Cyclic Peptide Nanotubes at the Water/Hexane Interface

“…6 For example, the backbone of a CHP with hydrophilic side chains may tilt toward the water phase, which largely weakens the lateral diffusion and rotational motion of the CHP at the interface. 6 A CPNT formed from the self-assembly of amino acids possesses a hollow tubular structure 7,8 and favorable biocompatibility 9−13 and exhibits distinctive characteristic of effectively transporting molecules and ions, i.e., water, 14,15 O 2 , CO 2 , 16,17 and K + , Na + , Ca 2+ . 18−20 Amino acids with different residues endow the external surface of a CPNT with diverse hydrophilicity/hydrophobicity.…”

“…A CPNT formed from the self-assembly of amino acids possesses a hollow tubular structure , and favorable biocompatibility − and exhibits distinctive characteristic of effectively transporting molecules and ions, i.e., water, , O 2 , CO 2 , , and K + , Na + , Ca 2+ . − Amino acids with different residues endow the external surface of a CPNT with diverse hydrophilicity/hydrophobicity. ,, The surface hydrophilicity/hydrophobicity of a nanoparticle may significantly affect its behavior at a water/oil interface. ,, The stability of a CPNT in a solvent is related to the structures of amino acid residues and the kind of the solvent, etc. MD simulation results demonstrated that the CPNTs with different surface polarities, 8 × cyclo-( W L) 4 and 8 × cyclo-(Q A E A ) 2 (E: glutamate), are more stable in a nonpolar solvent than in a polar solvent .…”