The effects of amino acid sequence and solvent polarity on the self-assembling of cyclic peptide nanotubes and molecular channel formation inside the lipid bilayer

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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en

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12

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Journal of Molecular Liquids, Volume 314

Abstract

In this article, the effects of amino acid sequence and solvent polarity on the self-assembling process of cyclic peptides (CPs) were investigated by employing molecular dynamic (MD) simulations and quantum chemistry calculations. As a result, CP dimers are not stable in water, because of hydrogen bond (H-bond) lost between the CP units, while chloroform increases the stability of the CP dimers. MM-PBSA and MM-GBSA calculations confirmed that solvent polarity has an important effect on the stability of the CP dimers. Dynamical behavior of the cyclic peptide nanotubes (CPNTs) in chloroform indicates that CPNTs composed of leucine and phenylalanine are better molecular containers than that of isoleucine. At the next step, the ability of these CPNTs in molecular channel formation inside a fully hydrated DMPC (dimyristoylphosphatidylcholine) bilayer was investigated during 50 ns MD simulations. The obtained results show that only CPNT composed of isoleucine can form a molecular channel inside the DMPC membrane because isoleucine has a greater hydrophobicity than leucine and phenylalanine. This property increases the interactions between the CPNT and lipid residues, which elevates the stability of the CPNT inside the DMPC bilayer. Quantum chemistry calculations and non-covalent interactions analysis indicate that the solvent changes the stability and dynamical behavior of the CPNTs through the change in the H-bond strength. Finally, according to the different analyses, it can be concluded that the amino acid sequence in the CP units has an important role in designing specific nanostructures.

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Khavani Sariani, M, Izadyar, M & Housaindokht, M R 2020, 'The effects of amino acid sequence and solvent polarity on the self-assembling of cyclic peptide nanotubes and molecular channel formation inside the lipid bilayer', Journal of Molecular Liquids, vol. 314, 113660. https://doi.org/10.1016/j.molliq.2020.113660