PROTON TRANSPORT ACROSS TRANSIENT SINGLE-FILE WATER PORES IN A LIPID-MEMBRANE STUDIED BY MOLECULAR-DYNAMICS SIMULATIONS

To test the hypothesis that water pores in a lipid membrane mediate th e proton transport, molecular dynamic simulations of a phospholipid me mbrane, in which the formation of a water pore is induced, are reporte d, The probability density of such a pore in the membrane was obtained from the free energy of formation of the pore, which was computed fro m the average force needed to constrain the pore in the membrane, It w as found that the free energy of a single file of water molecules span ning the bilayer is 108(+/- 10) kJ/mol, From unconstrained molecular d ynamic simulations it was further deduced that the nature of the pore is very transient, with a mean lifetime of a few picoseconds. The orie ntations of water molecules within the pore were also studied, and the spontaneous translocation of a turning defect was observed. The combi ned data allowed a permeability coefficient for proton permeation acro ss the membrane to be computed, assuming that a suitable orientation o f the water molecules in the pore allows protons to permeate the membr ane relatively fast by means of a wirelike conductance mechanism, The computed value fits the experimental data only if it is assumed that t he entry of the proton into the pore is not rate limiting.