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

Yongil Seo, Yeonho Song, George C Schatz, Hyonseok Hwang

Research output: Contribution to journalArticle

Abstract

The transport behavior of glucose through a cyclic peptide nanotube (CPN), composed of 8 × cyclo[-(Trp-d-Leu)4-Gln-d-Leu-] rings embedded in DMPC lipid bilayers was examined using all-Atom molecular dynamics (AAMD) simulations. Two conformational isomers of β-d-glucose, equatorial (4C1) and axial (1C4) chair conformers, were used to examine conformational effects on the hydrogen bond network, energetics, and diffusivity of glucose transport through the CPN. Calculations of the number of hydrogen bonds of the two glucose conformers with water molecules and with the CPN illustrate that the total number of hydrogen bonds of the conformers decreases inside the channel compared to bulk water due to the confinement characteristics of the interior of the CPNs although new hydrogen bonds between the hydroxyl and hydroxymethyl hydrogens of glucose and the carbonyl oxygens in the CPN backbone are formed. Despite the decrease of the number of hydrogen bonds inside the CPN, intramolecular hydrogen bonds of 1C4 are maintained during permeation of 1C4 through the CPN. The retention of intramolecular hydrogen bonds and the spherical shape of 1C4 give rise to considerably weaker orientational preferences and higher diffusion coefficients for 1C4 than those of 4C1 inside and outside the CPN. Due to larger dipole moments induced by the alignment of hydroxyl and hydroxymethyl groups, 1C4 has more favorable interactions with the CPN backbone at the channel entrances and inside the channel than 4C1. In the middle of the CPN channel, entropic gains originating from higher orientational and translational degrees of freedom of 1C4 than those of 4C1 also contribute to lower free energy wells for 1C4 inside the CPN. This work reveals that the conformational variation and intramolecular hydrogen bond formation of β-d-glucose can have important effects on the energetics and dynamics of glucose transport through CPNs, providing insight into the translocation mechanism of d-glucose into the cell through glucose transporters (GLUTs) and the dynamics of glucose confined in silica nanochannels. It is also demonstrated that CPNs can indeed facilitate the permeation of small hydrophilic molecules such as glucose and can be utilized as a novel carrier system for hydrophilic drug compounds into the cell.

Original languageEnglish
Pages (from-to)8174-8184
Number of pages11
JournalJournal of Physical Chemistry B
Volume122
Issue number34
DOIs
Publication statusPublished - Aug 30 2018

Fingerprint

Peptide Nanotubes
Cyclic Peptides
glucose
Nanotubes
peptides
Glucose
Molecular dynamics
nanotubes
molecular dynamics
Hydrogen bonds
Computer simulation
hydrogen bonds
simulation
Permeation
Hydroxyl Radical
Dimyristoylphosphatidylcholine
Molecules
Lipid bilayers
Facilitative Glucose Transport Proteins
Water

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube : A Molecular Dynamics Simulation Study. / Seo, Yongil; Song, Yeonho; Schatz, George C; Hwang, Hyonseok.

In: Journal of Physical Chemistry B, Vol. 122, No. 34, 30.08.2018, p. 8174-8184.

Research output: Contribution to journalArticle

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