A molecular dynamics investigation on transporting mechanism of glucose through a cyclic peptide nanotube

Abstract

Cyclic peptide nanotubes (CPNTs) are open-ended, hollow, and tubular structures that are made of several cyclic peptide rings. These structures can act as a transmembrane channel and transport ions or small molecules. In this work, we studied the stability of a cyclic peptide nanotube 8 × [(Trp-D-Leu)4-Gln-D-Leu] into a fully hydrated membrane composed of DPPC/POPC/POPS/cholesterol and also the transport mechanism of β-D-glucose through this nanotube was investigated. Our findings revealed that the CPNT was stable in the lipid bilayer during the simulation time and non-bonded interactions, especially hydrogen bonding have an important role to form a stable CPNT in the membrane. The glucose jumps from a Cα-region into the mid-Cα region and spends more time in this region because of its more desirable interactions with water molecules and the CPNT. In the transport pathway, non-bonded interactions between glucose, water molecules and the CPNT facilitate the transport of the glucose through the CPNT. The collaboration of hydrogen bonds, electrostatic and van der Waals interactions change the pulling force and lead to transport glucose through the CPNT. Potential of mean force (PMF) calculations revealed that the glucose has a minimum value of binding free energy and maximum configurational entropy in MPR regions. These findings can be used to design more CPNTs with different goals such as drug delivery. Communicated by Ramaswamy H. Sarma