Molecular Dynamics Simulations on the Behaviors of Hydrophilic/Hydrophobic Cyclic Peptide Nanotubes at the Water/Hexane Interface

Abstract

In this work, nine kinds of amino acid residues, i.e., alanine (A), leucine (L), valine (V), isoleucine (I), tryptophan (W), glutamine (Q), threonine (T), serine (S), and cysteine (C), were selected to construct seven cyclic peptide nanotubes (CPNTs) with diverse hydrophilic/hydrophobic external surfaces, which were further separately inserted at the water/hexane interface to investigate their microstructures and interfacial properties. Molecular dynamics (MD) simulations reveal that all the CPNTs except the QT- and VL-CPNTs have different degrees of tilt, fracture, and shedding at the interface. The end-CPs are more susceptible to the effect of the surroundings than the mid-CPs. The interactions of individual CP subunits with the neighborings disclose the firmness of the mid-CPs and the dissociation of the end-CPs. The results indicate that a hydrophobic CPNT is prone to stay at the interface, while a hydrophilic CPNT easily enters the water phase, resulting in many H-bonds with water. Results in this work enrich the dynamic properties of a hydrophilic/hydrophobic CPNT at the biphase interface at the atomic level.

Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison

“…Some approaches have been made in this direction in order to reproduce the conformational properties of a model CP [ 21 , 22 , 23 ], but there is a significant literature gap in the simulation of SCPNs with different force fields. Peptide nanotubes composed of D , L -α-CPs have been simulated using mainly the CHARMM [ 24 , 25 , 26 , 27 , 28 ] and AMBER [ 29 , 30 , 31 ] force fields. However, an exhaustive force field comparison is still missing, and is crucial in order to evaluate their influence on the structural and dynamic properties of these systems.…”