Study on the Assembly Mechanisms and Transport Properties of Transmembrane End-Charged Cyclic Peptide Nanotubes

• Published in: Journal of chemical information and modeling Vol. 61; no. 6; pp. 2754 - 2765
• Main Authors: Gong, Ting, Fan, Jianfen
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 28.06.2021
• Subjects: Assembling; Chains; Computational Chemistry; Density functional theory; Ion channels; Molecular dynamics; Nanotubes; Peptides; Transport properties
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.1c00194

In this work, two end-charged cyclic peptide nanotubes (CPNTs) embedded in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) were designed to simulate transmembrane ion channels. Density functional theory (DFT) computations at the level of M06-2X/6-31G give different assembling modes of the negatively charged ELWL–CPNT and positively charged RLWL–CPNT as (L–L)­(D–L)­(D–D)­(L–L)­(D–D)­(L–L)­(D–D) and (D–D)­(L–L)­(D–D)­(L–L)­(D–D)­(L–L)­(D–D), respectively. Molecular dynamics (MD) simulations indicate that a charge at a CPNT end obviously affects the structure of the channel water chain and the diffusion behavior of K+. The regions with the highest probability of H-bond defects in the channel water chains are gap5 and gap2 in ELWL/POPE–CPNT and RLWL/POPE–CPNT, respectively. K+ can easily enter either CPNT by desolvation, and behaves more actively in RLWL/POPE–CPNT, shuttling rapidly and frequently between an α-plane zone and an adjacent midplane region. Results of this work reveal that a charge at the end of an ionic channel may significantly alter the transport characteristics of the channel.