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

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