Transprotein-Electropore Characterization: A Molecular Dynamics Investigation on Human AQP4

Abstract

Electroporation characterization is a topic of intensive interest probed by extensive ongoing research efforts. Usually, these studies are carried out on lipid-bilayer electroporation. Surprisingly, the possibility of water-channel electropore formation across transmembrane proteins themselves, particularly in view of such a promising application, has not yet been elucidated. The present work examines the geometrical and kinetic aspects of electropores and their stability in such a protein milieux (as opposed through the phospholipid membranes) in depth, by means of scrutiny of such a process in human-AQP4 as a well-representative prototype. The residues forming the electropore’s walls, organized in loops, reveal the formation mechanism by their dipole alignment and translational response in response to applied axial electric fields in nonequilibrium molecular dynamics simulation. The magnitude of sustaining electric fields (keeping a stable electropore open) were determined. This suggests that transmembrane proteins could play a central role in electroporation applications, e.g., in medicine and biotechnology.

Pulsed Electric Fields Can Create Pores in the Voltage Sensors of Voltage-Gated Ion Channels

“…Our conclusions are mainly built on analyses of protein hydration and electrostatic profiles, which can be straightforwardly performed on other membrane proteins. In this regard, a recent MD study on a human aquaporin has revealed the formation of a transient electric-field-induced pore through this protein; unlike the complex pores observed in our simulations, this pore closed within ∼20 ns after turning off the electric field ( 75 , 76 ). In our work, we additionally reported conduction of ions through the central channel pore in the NavMs structure, which was presumably solved in an open state.…”

Pulsed electric fields create pores in the voltage sensors of voltage-gated ion channels

“…Our conclusions are mainly built on the analyses of protein hydration and electrostatic profiles, which can be straightforwardly performed on other membrane proteins. In this regard, a recent MD study on a human aquaporin has revealed formation of a transient electric-field induced pore through this protein; unlike the complex pores observed in our simulations, this pore closed within about 20 ns after turning off the electric field (71,72). In our work we additionally reported conduction of ions through the central channel pore in the NavMs structure, which was presumably solved in an open state.…”

Electro-opening of a microtubule lattice in silico

“…Most of the investigations have been performed in silico [22] , where they explored either membrane [23] or protein systems. The effect of the electric field was mostly on the secondary structure, conformation, and orientation of various proteins [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , including cytoskeletal system proteins such as tubulin [43] , [44] , [45] , [46] , [47] and kinesin [48] , even leading to the unfolding of some proteins [49] , [50] , [51] . Most of this work explored electric field effects either in a single protein or membrane-bound proteins systems.…”