Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

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

doi:10.1039/c2cp42038d

Cited by 32 publications

(30 citation statements)

References 68 publications

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“…8 For example, Subramanian and co-workers investigated the ability of some CPNTs to transport the antitumor drug 5-fluorouracil across a lipid bilayer. 9 Solvents and amino acid composition are important parameters involved in the stability of CPNT structures. Previous theoretical studies indicate that these structures are more stable in nonpolar solvents.…”

Section: Introductionmentioning

confidence: 99%

A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes

Izadyar

Khavani

Housaindokht

2015

Phys. Chem. Chem. Phys.

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Molecular dynamic simulations were performed to investigate the stability of heterocyclic peptide nanotubes composed of 1,4-disubstituted-1,2,3-triazol ε-amino acid. 45 ns MD simulations were conducted on the cyclic peptide nanotube (CPNT) and cyclic peptide dimer in methanol, chloroform, and water and revealed that these structures are more stable in nonpolar solvents. MM-PBSA and MM-GBSA calculations were employed to analyze the solvent effect on the stability and length of the CPNT. These calculations showed that CPNT in chloroform was more stable and longer as compared to other solvents. In addition, the effect of the guest molecule (ethanol) inside the dimer and CPNT was investigated. The obtained results confirmed that guest molecule(s) stabilized the dimer and CPNT in all solvents. Quantum chemistry calculations on the cyclic peptide dimer were performed at the M06-2X/6-31G(d) level in the gas phase and three solvents. The obtained results from the quantum chemistry study were in good agreement with the MD simulation results. DFT calculations showed that the guest molecule stabilized the dimer structure and electrostatically interacted with the cyclic peptide dimer. Finally, for investigation of the solvent effects on the hydrogen bonds of the cyclic peptide dimer, NBO and AIM analysis were performed.

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Section: Introductionmentioning

confidence: 99%

A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes

Izadyar

Khavani

Housaindokht

2015

Phys. Chem. Chem. Phys.

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“…For this purpose, the RDF of each selected atom of the LA relative to a reference atom was calculated at each step of SMD simulation, and then the average of the calculated RDFs was obtained. The RDF shows the probability of finding specific atoms close to a reference group. ,, The fundamental characteristic of competition between water molecule and the enantiomers for binding to the CPNT is the main reason for transferring LA through the CPNT . LA can interact with water molecules through its oxygen and hydrogen atoms.…”

Section: Results and Disscusionmentioning

confidence: 99%

Transport Behavior of the Enantiomers of Lactic Acid through the Cyclic Peptide Nanotube: Enantiomer Discrimination

2017

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The behavior and mechanism of the transport of the enantiomers of lactic acid (LA) in a cyclic peptide nanotube (CPNT) embedded in water, consisted of eight cyclic peptide unit ([Ala-d-Ala-L]5), have been studied in details using quantum calculations and steered molecular dynamic (SMD) simulations, separately. The SMD simulations were performed in three different phases, and it was observed that the transport behavior of two enantiomers in the CPNT is different from each other in each phase. The variation of the calculated pulling force of two enantiomers versus time in three phases showed that (a) if the enantiomers move near the walls of CPNT, the velocity of S-enantiomer is more than R-enantiomer and the walls of the nanotube can act as chirality discriminator, (b) if the enantiomers are limited to move in the center of CPNT the velocity of R-enantiomer is more than S-enantiomer, and (c) when the enantiomers move in the nanotube and their center of mass is free for the displacement in the x and y directions as well as displacement in the z-direction, again the velocity of R-enantiomer is higher than S-enantiomer. The radial distribution functions (RDFs) of the important atoms of the enantiomers, relative to the O atoms of CNPT, were calculated, and it was observed that the affinities of the atoms of two enantiomers to O atoms of CNPT during their movement in the CPNT are different in each phase. The results obtained in this work typically show that the transportations of the enantiomers of biological molecules moving in the biological channels are different.

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“…During the SMD simulations, the force was only applied along the pulling direction [ 33 ]. The spring constant was set to the value of 2000 kJ mol-1 nm-2 and the pulling velocity to 0.0008 nm ps-1 [ 34 ]. The time length for each simulation was set to 5ns to ensure the complete unbinding of the peptide from the receptor.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of peptide designing strategy against subunit reassociation in mucin 1: A steered molecular dynamics approach

2017

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Subunit reassociation in mucin 1, a breast cancer tumor marker, is reported as one of the critical factors for its cytoplasmic activation. Inhibition of its heterodimeric association would therefore result in loss of its function and alter disease progression. The present study aimed at evaluating peptide inhibitor designing strategies that may serve as antagonist against this receptor-ligand alliance. Several peptides and their derivatives were designed based on native residues, subunit interface, hydrogen bonding and secondary structure. Docking studies with the peptides were carried on the receptor subunit and their binding affinities were evaluated using steered molecular dynamics simulation and umbrella sampling. Our results showed that among all the different classes of peptides evaluated, the receptor based peptide showed the highest binding affinity. This result was concurrent with the experimental observation that the receptor-ligand alliance in mucin 1 is highly specific. Our results also show that peptide ligand against this subunit association is only stabilized through native residue inter-protein interaction irrespective of the peptide structure, peptide length and number of hydrogen bonds. Consistency in binding affinity, pull force and free energy barrier was observed with only the receptor derived peptides which resulted in favorable interprotein interactions at the interface. Several observations were made and discussed which will eventually lead to designing efficient peptide inhibitors against mucin 1 heterodimeric subunit reassociation.

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Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

Cited by 32 publications

References 68 publications

A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes

A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes

Transport Behavior of the Enantiomers of Lactic Acid through the Cyclic Peptide Nanotube: Enantiomer Discrimination

Evaluation of peptide designing strategy against subunit reassociation in mucin 1: A steered molecular dynamics approach

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