Investigation of structures and properties of cyclic peptide nanotubes by experiment and molecular dynamics

Zhu, Jingchuan; Cheng, Jie; Liao, Zhouxiong; Lai, Zhonghong; Liu, Bo

doi:10.1007/s10822-008-9212-9

Cited by 33 publications

(33 citation statements)

References 51 publications

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“…(29) Such a hydrogen bond network in our ortho -CPN was relatively persistent during the course of CMD simulation. Interestingly, the side chains of the eight intersubunit peptides rearranged their orientations and have led to the formation of a new hydrogen bond network in consecutive rings, particularly between l -Trp and l -Gln or between l -Gln and l -Gln.…”

Section: Resultsmentioning

confidence: 88%

Molecular Insights on the Cyclic Peptide Nanotube-Mediated Transportation of Antitumor Drug 5-Fluorouracil

et al. 2010

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Self-assembled cyclic peptide nanotubes (CPNs) show a potential use in drug delivery. In this study, the CPN composed of (Trp-d-Leu)4-Gln-d-Leu was synthesized and tested for the transport of the antitumor drug 5-fluorouracil (5-FU). CPN-mediated release of 5-FU from liposomes experimentally tested the transportation function of the synthetic CPNs. To explore the transportation mechanism of CPNs, computational studies have been performed on the CPN models stacked by 8 subuints, including conventional molecular dynamics (CMD) simulations, and steered molecular dynamics (SMD) simulations in the environment of hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer. Our CMD simulations demonstrated that the ortho-CPN is the most stable nanotube, in which the Gln residue is in the ortho-position relative to other residues. The calculated diffusion coefficient value for inner water molecules was 1.068 × 10−5 cm2·s−1, almost half that of the bulky water and 24 times faster than that of the typical gramicidin A channel. The CPN conserved its hollow structure along the 10 ns CMD simulations, with a tile angle of 50° relative to the normal of DMPC membrane. Results from SMD simulations showed that the 5-FU molecule was transported by hopping through different potential energy minima distributed along subunits, and finally exited the nanotube by escaping from the kink region at the last two subunits. The hopping of 5-FU was driven by switching from hydrophobic interactions between 5-FU and the interior wall of the nanotube to hydrogen bonding interactions of 5-FU with the backbone carbonyl group and amide group of ortho-CPN. The calculated binding free energy profile of 5-FU interacting with the CPN indicated that there was an energy well near the outer end of the nanotube.

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Section: Resultsmentioning

confidence: 88%

Molecular Insights on the Cyclic Peptide Nanotube-Mediated Transportation of Antitumor Drug 5-Fluorouracil

et al. 2010

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“…For the motion behaviour of water molecules in a cyclo[(-D-Phe-L-Ala) n¼4 À ] peptide nanotube, Zhu et al (2008) use a COMPASS force field to show that due to the stacking arrangement of antiparallel rings, water molecules do not diffuse unilaterally, but do so in one dimension. Song et al (2013) study the dynamics of Na þ transportation in a cyclic peptide nanotube of 8 Â(WL) 4 /POPE that contains water molecules.…”

Section: Introductionmentioning

confidence: 99%

Modelling water molecules inside cyclic peptide nanotubes

2015

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Cyclic peptide nanotubes occur during the selfassembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(-DAla-L-Ala) 4 -] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1 À 2 À 1 À 2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

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“…CPNs with inner diameter ranging from 5.9 to 13.1 Å can be readily achieved by selecting the number of amino acid subunits. [18] The fabrication of sub-nanometer porous membranes remains challenging using conventional techniques, [2] and therefore the design of a biological membrane using a polymerizable LLC system in conjunction with CPNs could potentially help to overcome current fabrication limitations. Recently, we showed that the nanostructured domains presented in LLC systems could be used to align CPNs in a similar manner to that of protein membranes in biological membrane.…”

Section: Doi: 101002/macp201800307mentioning

confidence: 99%

Impact of Comonomer Chemistry on Phase Behavior of Polymerizable Lyotropic Ionic Liquid Crystals: A Pre‐ and Post‐Polymerization Study

Goujon

Dumée

Byrne

et al. 2018

Macro Chemistry & Physics

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The design and characterization of polymerizable lyotropic ionic liquid crystals with an intact alkyl chain bilayer are described. The bilayer is left intact to enable further inclusion of peptide‐based channels to mimic biological protein membranes for potential separation applications. Impact of comonomer concentration and chemistry on the mesophase formed pre‐ and post‐polymerization is characterized. An optimum comonomer concentration of 20 wt% is found for the poly(ethylene glycol) diacrylate (PEGDA) system, before full disruption of the discontinuous cubic phase occurs. Little impact on the discontinuous cubic phase is observed by varying comonomer chemistry from PEGDA to either poly(ethylene glycol) dimethacrylate or 2‐hydroxyethyl acrylate, with exception of variation in the thermal stability of the resulting mesophase. Surprisingly, the use of 2‐hydroxyethyl methacrylate as comonomer results in formation of the 2D hexagonal phase, which is of interest for the design of biological protein membranes. Unfortunately, mesostructure retention is not observed in any systems studied. A sequence of structural changes, modeled as a change from a spherical micelle to a cylindrical micelle, and to finally a lamellar architecture, is rather observed using in situ small‐angle X‐ray scattering polymerization measurements, suggesting a reduction of the headgroup area, likely caused by cross‐linking of the acrylate moiety.

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Investigation of structures and properties of cyclic peptide nanotubes by experiment and molecular dynamics

Cited by 33 publications

References 51 publications

Molecular Insights on the Cyclic Peptide Nanotube-Mediated Transportation of Antitumor Drug 5-Fluorouracil

Molecular Insights on the Cyclic Peptide Nanotube-Mediated Transportation of Antitumor Drug 5-Fluorouracil

Modelling water molecules inside cyclic peptide nanotubes

Impact of Comonomer Chemistry on Phase Behavior of Polymerizable Lyotropic Ionic Liquid Crystals: A Pre‐ and Post‐Polymerization Study

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