Structure and stability of cyclic peptide based nanotubes: a molecular dynamics study of the influence of amino acid composition

Vijayaraj, R.; Damme, Sofie Van; Bultinck, Patrick; Subramanian, V.

doi:10.1039/c2cp42030a

Cited by 21 publications

(30 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2)c, which is higher for the AFCP sequence than for the original CP sequence. This can be explained by the formation of H-bonds between hydroxyl groups in adjacent side-chains, as predicted by Vijayaraj et al 11 . Indeed, when increasing the AFCP nanotube size from CPNT2 to CPNT3, we hypothesize that the hydroxyl groups of threonine side-chains interact less strongly with water molecules while forming more side chain intramolecular hydrogen bonds, thus decreasing the RMSFs of AFCP sequence CPNTs similar to the original CP sequence RMSF levels.…”

Section: Cpnt2mentioning

confidence: 54%

“…The geometry of each single CP unit was energy minimized using steepest descent while the Ramachandran dihedral angles (Φ, Ψ) of all amino acids were restrained to their average anti-parallel β-sheet values as given in Table 1, in order to guarantee the planarity of the ring. Since the side chains of the cyclic peptides play a crucial role in the stability of the nanotubes 11 , also the side chains of the rings were relaxed in a 10 ns NPT simulations.…”

Section: Construction Of the Cyclic Peptides And Nanotubesmentioning

confidence: 99%

“…1 top left. Experiments 8,9 and simulations 10,11 indicate that cyclic peptides of alternating L and D amino acids self-assemble into nanotubes under proper conditions. These nanotubes consist of an anti-parallel cyclic β-sheet hollow structure, stabilized by backbone hydrogen bonds between adjacent CPs and by side chain interac-tions 11 (see Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1bottom). Vijayraj et al 10,11 investigated the number of required CPs for a stable nanotube, and showed the importance of alanine (ALA) amino acids in the stability and fluctuations of the nanotube. Introducing an ice binding motif sequence in such cyclic peptides could lead to self-assembled nanotubes with great potential as an anti-freeze agent.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stability and growth mechanism of self-assembling putative antifreeze cyclic peptides

Brotzakis

Gehre

Voets

et al. 2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Cyclic peptides (CPs) that self-assemble in nanotubes can be candidates for use as antifreeze proteins. Based on the cyclic peptide sequence cyclo-[(l-LYS-d-ALA-l-LEU-d-ALA)], which can stack into nanotubes, we propose a putative antifreeze cyclic peptide (AFCP) sequence, cyclo-[(l-LYS-d-ALA)-(l-THR-d-ALA)], containing THR-ALA-THR ice binding motifs. Using molecular dynamics simulations we investigate the stability of these cyclic peptides and their growth mechanism. Both nanotube sequences get more stable as a function of size. The relative stability of the AFCP sequence CPNT increases at sizes greater than a dimer by forming intermolecular THR side chain H-bonds. We find that, like the naturally occurring AF protein from spruce budworm (Choristoneura fumiferana), the THR distances of the AFCP's ice binding motif match the ice prism plane O-O distances, thus making the AFCP a suitable AF candidate. In addition, we investigated the nanotube growth process, i.e. the association/dissociation of a single CP to an existing AFCP nanotube, by Transition Path Sampling. We found a general dock-lock mechanism, in which a single CP first docks loosely before locking into place. Moreover, we identified several qualitatively different mechanisms for association, involving different metastable intermediates, including a state in which the peptide was misfolded inside the hydrophobic core of the tube. Finally, we find evidence for a mechanism involving non-specific association followed by 1D diffusion. Under most conditions, this will be the dominant pathway. The results yield insights into the mechanisms of peptide assembly, and might lead to an improved design of self-assembling antifreeze proteins.

show abstract

Section: Cpnt2mentioning

confidence: 54%

Section: Construction Of the Cyclic Peptides And Nanotubesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stability and growth mechanism of self-assembling putative antifreeze cyclic peptides

Brotzakis

Gehre

Voets

et al. 2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

“…Atomistic simulations on assembled peptides have been extensively reported in the past decade, [42][43][44][45][46][47][48] with the results allowing us not only to get microscopic information about the association process at both kinetic and thermodynamic levels but also to complement experimental information. Despite such valuable contributions, atomistic computer simulations on peptide-polymer conjugates have been frequently restricted to the examination of the behaviour of individual molecules (i.e.…”

mentioning

confidence: 99%

Atomistic organization and characterization of tube-like assemblies comprising peptide–polymer conjugates: computer simulation studies

et al. 2013

View full text Add to dashboard Cite

The structure and stability of the nanotube obtained by assembling peptidepolymer conjugates consisting of two poly(n-butyl acrylate) blocks coupled tohave been investigated at the molecular level using atomistic molecular dynamics simulations. The effect of the wrapping polymer shells in the tube-like core, which consists of stacked b-sheet cyclopeptides, has been examined by simulating assemblies of both unsubstituted cyclopeptides, and conjugates in chloroform and N,N-dimethylformamide solutions. Furthermore, the influence of the environment has been investigated by comparing conjugate assemblies in solution with those deposited on mica. In addition, nanotubes stabilized by b-sheet-like hydrogen bonds between both parallel and antiparallel oriented cyclopeptides have been considered in all cases. The results, which have been analysed in terms of energy contributions, partial radial distribution functions, inter-subunit distances, shape of the cyclopeptide ring, internal van der Waals diameters, and both height and width of the nanostructures deposited on mica, have provided important microscopic insights. For example, analysis of both the energy terms and the structural dynamics obtained for the different assemblies indicate that the mica surface interacts more favourably with the parallel assembly than with the antiparallel ones, whereas the only configuration that is structurally stable in solution is the latter. Furthermore, adsorption onto the solid substrate produces a small deformation of the cylindrical molecular system.

show abstract

A Practical Guide to Structural Aspects of Macrocycles (NMR, X‐Ray, and Modeling)

Craik

Kaas

Wang

2017

Practical Medicinal Chemistry With Macrocycles

View full text Add to dashboard Cite

Structure and stability of cyclic peptide based nanotubes: a molecular dynamics study of the influence of amino acid composition

Cited by 21 publications

References 44 publications

Stability and growth mechanism of self-assembling putative antifreeze cyclic peptides

Stability and growth mechanism of self-assembling putative antifreeze cyclic peptides

Atomistic organization and characterization of tube-like assemblies comprising peptide–polymer conjugates: computer simulation studies

A Practical Guide to Structural Aspects of Macrocycles (NMR, X‐Ray, and Modeling)

Contact Info

Product

Resources

About