All-atom molecular dynamics simulations of an artificial sodium channel in a lipid bilayer: the effect of water solvation/desolvation of the sodium ion

Abstract

All-atom molecular dynamics is used to investigate the transport of Na(+) across a 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayer facilitated by a diazacrown hydraphile. Specifically, the free energy of Na(+) passing through the bilayer is calculated using the adaptive biasing force method to study the free energy associated with the increase in Na(+) transport in the presence of the hydraphile molecule. The results show that water interaction greatly influences Na(+) transport through the lipid bilayer as water is pulled through the bilayer with Na(+) forming a water channel. The hydraphile causes a reduction in the free energy barrier for the transport of Na(+) through the head group part of the lipid bilayer since it complexes the Na(+) reducing the necessity for water to be complexed and, therefore, dragged through with Na(+), an energetically unfavorable process. The free energy associated with Na(+) being desolvated within the bilayer is significantly decreased in the presence of the hydraphile molecule; the hydraphile increases the number of solvation states of Na(+) that can be adopted, and this increase in the number of available configurations provides an entropic explanation for the success of the hydraphile.

Quantum mechanical calculations of the interactions between diazacrowns and the sodium cation: an insight into Na+ complexation in diazacrown-based synthetic ion channels

“…Our previous work suggested that when the number of solvent states increases, there are a greater number of mechanisms that are available for transport of Na + and this could mean that the transport process is more likely. 67 (2) There is hydrogen bonding between the diazacrown oxygen and nitrogen atoms and water and this may be responsible for water ordering and channel forming in the hydraphile as proposed by Murray et al 22 The presence of Na + within the diazacrown actually strengthens the water diazacrown interaction and this may be a factor in the ordering of water. The ordering of water molecules and reduction of rotational entropy may offset this effect, however.…”

“…The force eld used in this study was the one used in our previous work; 67 however, in that study, dihedral parameters were not included and in this case, when geometryoptimizations of the diazacrown were performed, there was a visible discrepancy between QM and force eld geometries. For this reason the dihedral parameters were added.…”

“…Force eld calculations show that the diazacrown nitrogen atom to Na + distances are increased (by 0.14 Å) and diazacrown oxygen atom to Na + distance decreased (by 0.05 Å) compared to QM results. In our previous work, 67 the radial distribution function (RDF) of Na + to diazacrown oxygen and nitrogen atoms, as Na + was pulled through a DMPC lipid bilayer, whilst complexed with the terminal diazacrown of the hydraphile, was reported. It showed that the Na + to diazacrown oxygen distance centered at 2.3 Å (ranging from 2-2.7 Å) but the Na + to diazacrown nitrogen atom distance appeared at much greater distances (ranging from 3.6 to 4.6 Å).…”

Dynamical Properties of Water and Ions at the Quartz (101)–Water Interface at a Range of Solution Conditions: A Classical Molecular Dynamics Study

“…Apart from controlling the drug release, the dynamics of the interfacial water should be critical for the effectiveness of the administered MSN within the body, controlling the in vivo biodistribution and bioavailability, which depend on the colloidal properties. Moreover, the interaction the MSNs with biomolecules, such as plasma proteins and lipid molecules within cell membranes, involves mediation by the structured water molecules and ions. − …”

Synthetic ionophores as non-resistant antibiotic adjuvants

“…17 The channels that most effectively conduct alkali metal cations 14 have C n chains of 12-16 methylenes. 18,19 These bilayer-spanning amphiphiles transport Na + ions through liposomes 16 and exhibit antibacterial properties. 4 We previously reported that BC 14 H, when co-administered at sublethal concentrations, enhances the efficacy of erythromycin, kanamycin, rifampicin, and tetracycline against drug-sensitive E. coli, Pseudomonas aeruginosa, and Bacillus subtilis.…”