A novel molecular dynamics study of CO2 permeation through aquaporin-5.

Aquaporins (AQPs) are protein channels which facilitate rapid water permeation across cell membrane. The AQPs are very vital for biological organs, as their malfunction causes severe diseases in human body. A particular family of AQPs, that is AQP5, has a significant role in lung fluid transport due to submucosal glands structure. However, it has not been yet well understood whether these protein channels can conduct gas molecules. Here, Molecular Dynamics (MD) simulations are used to investigate the CO2 permeability and diffusion in AQP5 during a 40-nanosecond period. For the first time, equilibrium and Steered MD (SMD) are used to simulate self and force-induced diffusion of CO2 molecules across AQP5 and POPE lipid bilayer. According to PMFs profile associated to CO2 permeation, the hydrophobic central pore provides a more suitable pathway for gas molecules compared to other AQP5 channels. Although CO2 molecules can also permeate across AQP5 water channels, the rate of CO2 permeation through four channels of the AQP5 monomers is much lower than the central pore. The rate of CO2 permeation through four AQP5 water channels is even lower than CO2 diffusion through POPE lipid membrane. The results reported in this investigation demonstrate that MD simulations of human AQP5 provide valuable insights into the gas permeation mechanism for both the equilibrium self-diffusion, and quasi-equilibrium condition.

Forced diffusion of water molecules through aquaporin-5 biomembrane; a molecular dynamics study.

Aquaporins (AQPs) are protein channels located across the cell membrane which conduct the water permeation through the cell membrane. Different types of AQPs exist in human organs and play vital roles, as the malfunction of such protein membranes can lead to life-threatening conditions. A specific type of AQP, identified as AQP5, is particularly essential to the generation of saliva, tears and pulmonary secretions. We have adopted Molecular Dynamics (MD) simulation to analyze the water permeation and diffusion in AQP5 structure in a 0.5 microsecond simulation time window. The MD numerical simulation shows the water permeability of the human AQP5 is in the nominal range for other members of human aquaporins family. In addition, we have considered the effect of the osmotic water diffusion and the diffusion occurred by pressure gradient on the protein membrane. The water permeability grows monotonically as the applied pressure on the solvent increases. Furthermore, the forced diffusion increases the minimum radius of Selectivity Filter (SF) region of region AQP5 up to 20% and consequently the permeability coefficients enhance enormously compared to osmotic self-diffusion in AQP5 tetramer. Finally, it is revealed that the MD simulation of human AQP5 provides useful insights into the mechanisms of water regulation through alveolar cells under the different physical conditions; osmotic self-diffusion and forced diffusion condition.

Numerical investigation of molecular nano-array in potential-energy profile for a single dsDNA.

A Rigorous numerical investigation on dsDNA translocation in quasi-2-dimensional nano-array filter is performed using Molecular Dynamics (MD) method. Various dsDNA molecules with different sizes are chosen in order to model Ogston sieving in a nano-array filter. The radius of gyration of dsDNA molecule is less than the characteristic length of the shallow region in nano-array. The dsDNA molecule is assumed to be in the 0.05M NaCl electrolyte. MD shows acceptable results for potential-energy profile for nano-array filter. According to the MD outcomes, the dsDNA electrophoretic mobility decreases almost linearly with dsDNA size and show the same trend as Ogston sieving for gel electrophoresis. In addition, different shapes for nano-array filter are studied for a unique dsDNA molecule. It is concluded that steeping the nano-array wall can cause the retardation of dsDNA translocation and decreases dsDNA electrophoretic mobility.

Rigorous study of molecular dynamics of a single dsDNA confined in a nanochannel: Introduction of a critical mobility behaviour.

The essential and effective characteristics of a double-stranded DNA (dsDNA) confined in a nanochannel is revisited by employing the rigorous full numerical approach of Molecular Dynamics (MD). The deformation of dsDNA and wall-biomolecule interaction which is critical in highly confined regime has been precisely imposed in numerical simulations. The numerical approach has been justified against available theoretical outcomes. A new and general expression for DNA electrophoretic mobility versus DNA length is extracted from numerical simulation which is out of reach of experimental methods due to practical shortcomings. The newly derived expression suggests an essential correction in the previously proposed expression for the critical case of small DNA molecules and reveals an astonishingly unbeknown trend of small DNA's mobility. Sub-molecular phenomenon of dsDNA melting under the condition of large external force is also studied. Assuming strong electric field exertion, the MD approach aptly demonstrates the elaborate melting phenomenon for dsDNA in sub-molecular scale.