TY - JOUR
T1 - Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube
T2 - A Molecular Dynamics Simulation Study
AU - Seo, Yongil
AU - Song, Yeonho
AU - Schatz, George C.
AU - Hwang, Hyonseok
N1 - Funding Information:
National University (No. 520170531)
Funding Information:
This research was supported by Basic Science Research Program (No. NRF-2017R1D1A3B03028669) and by Basic Research Laboratory (No. NRF-2017R1A4A1015405) through the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST). This study was supported by 2017 Research Grant from Kangwon National University (No. 520170531). G.C.S. was supported by the Department of Energy, Office of Basic Energy Sciences, under the CBES EFRC, grant DE-SC0000989.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/8/30
Y1 - 2018/8/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052295219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052295219&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.8b05591
DO - 10.1021/acs.jpcb.8b05591
M3 - Article
C2 - 30086632
AN - SCOPUS:85052295219
VL - 122
SP - 8174
EP - 8184
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1520-6106
IS - 34
ER -