title: Deconstruction of the human connexin 26 hemichannel due to an applied electric field; A molecular dynamics simulation study.
abstract: Connexins are a 21-member membrane protein family constituting channels evolved in direct communication between adjacent cells by passaging cytoplasmic molecules and ions. Hexametrical assembly of connexin proteins in plasma membrane forms a wide aqueous pore known as connexin hemichannel. These hemichannels mediate cytoplasm and extracellular milieu communication both in many external tissues and in the central nervous system. In this study, a series of molecular dynamics simulations has been performed to investigate the effect of applied static and alternating electric fields on the stability and conformation of human connexin26 hemichannel. The root mean square deviations of C-alpha atoms, the dipole moment distribution, the number of inter-protein hydrogen bonds and the number of water-protein hydrogen bonds were used to assess connexin26 hemichannel stability. In the static field case, our results show that although the lowest field used in this study (0.1V/nm) does not lead to the hemichannel deconstruction, stronger fields (>0.1V/nm), however, disrupt the protein structure during the simulations time period. Furthermore, in the alternating case, compared to static field case, field effects on the connexin26 hemichannel conformation are reduced and consequently the protein maintains its native structure for longer times. Specifically, for the highest frequency used in this study (50GHz), the hemichannel keeps its structure even under the effect of the strongest field (0.4V/nm). According to our results, the protein secondary structure is preserved in the characteristic times determined for the protein deconstruction. Consequently, we suggest that the protein deconstruction is due to the tertiary and quaternary structure loss.
authors.affiliation: Department of Physics, Faculty of Sciences, University of Zanjan, Zanajn, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Alizadeh
authors.affiliation: Department of Physics, Faculty of Sciences, University of Zanjan, Zanajn, Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Davoodi
authors.affiliation: Department of Medical Physics and Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran. Electronic address: rafii-tabar@nano.ipm.ac.ir.
authors.forename: Hashem
authors.initials: H
authors.lastname: Rafii-Tabar
mesh_terms: D000072259:Connexin 26 / Q000737:chemistry*; D004560:Electricity; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D000072259:Connexin 26
keywords: Connexin 26; Electric fields effects; Molecular dynamics simulation; Protein deconstruction