Theory and Simulation of Water Permeation in Aquaporin-1

Abstract

We discuss the difference between osmotic permeability pf and diffusion permeability pd of single-file water channels and demonstrate that the pf/pd ratio corresponds to the number of effective steps a water molecule needs to take to permeate a channel. While pd can be directly obtained from equilibrium molecular dynamics simulations, pf can be best determined from simulations in which a chemical potential difference of water has been established on the two sides of the channel. In light of this, we suggest a method to induce in molecular dynamics simulations a hydrostatic pressure difference across the membrane, from which pf can be measured. Simulations using this method are performed on aquaporin-1 channels in a lipid bilayer, resulting in a calculated pf of 7.1 x 10(-14) cm(3)/s, which is in close agreement with observation. Using a previously determined pd value, we conclude that pf/pd for aquaporin-1 measures approximately 12. This number is explained in terms of channel architecture and conduction mechanism.

Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?

“…The method rests on the assumption that the permeation rate is proportional to a Boltzmann factor exp(−ΔG ‡ /k B T ) with an Arrhenius activation energy ΔG ‡ . (For an expanded derivation see Zhu et al 2004b.) For AQP1, the method was reported to yield p f = 7.5×10 14 cm 3 s −1 Grubmüller 2001, 2005) or 7.1×10 14 cm 3 s −1 (Zhu et al 2004b), in good agreement to experimental values of 3.2 to 11.7 × 10 14 cm 3 s −1 (Engel and Stahlberg 2002).…”

Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens

“…For a channel in which water molecules form a single file and translocate simultaneously, one can show that the ratio of p f to p d equals the average water occupancy plus one (35,36). We found Table 1 and SI Appendix), all significantly lower than the value of Ϸ11 (10 ϩ 1) expected if the single file were continuous.…”

“…Experimental evidence suggests that AQP0 exists in an equilibrium between weakly and highly conductive states, with the latter being favored at low pH (7,8). His-40, located in extracellular loop A (residues [33][34][35][36][37][38][39][40], is believed to function as the pH sensor, but the mechanism of pH regulation is not known (3).…”

Tunable sieving of ions using graphene oxide membranes

“…As at such interlayer spacings there is a large energy barrier associated with the entering of the ions into the channel (Table S2), we do not observe ion permeation over the typical timescale of a simulation. Therefore to calculate the ion permeation rates, a pressure difference of 10 MPa was applied across the simulation cell by adding a constant force on all of the atoms in the simulation box along the direction of the channel, except on those belonging to the graphene sheets [24][25][26][27] . During the simulations the temperature was maintained constant at 298.15 K. The interaction parameters for ion, water and graphene atoms were taken the same as the previous simulations.…”

“…The effective pore-size of 9 Å in these swollen membranes (excluding the space occupied by carbon atoms) is larger than a typical size of hydrated ions and restricts possible uses of GO for size-exclusion based ion sieving 19 . A number of strategies have been tried to inhibit the swelling effect, including partial reduction of GO 25 , ultraviolet reduction of GO-titania hybrid membranes 26 , and covalent crosslinking [27][28][29] . In this report, we investigate ion permeation through GO laminates with d controlled from ≈ 9.8 to ≈ 6.4 Å, which is achieved by physical confinement (Fig.…”