Promoting effect of ethanol on dewetting transition in the confined region of melittin tetramer

Nuclear Science and Techniques 23(2012)252- 256Promoting effect of ethanol on dewetting transition in the confinedregion of melittin tetramerREN XIuping" ZHOU Bo, WANG Chunle; lShanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, ChinaGraduate School of the Chinese Academy of Sciences, Beijing 100080, ChinaAbstract To study the influence of ethanol molecules on the melittin tetramer folding, we investigated the dewettingtransition of the melittin tetramer immersed in pure water and 8% aqueous ethanol solution(mass fraction) by themolecular dynamics simulations We found that the marked dewetting transitions occurred inside a nanoscale channelof the melittin tetramer both in puoted thdewetting transition. We attributed this promoting effect to ethanol molecules which prefer to locate at the liquidvapor interface and decrease the liquid-vapor surface energy. The results provide insight into the effect of ethanol onthe water dewetting phenomena.Key words Dewetting transition, Melittin tetramer, Ethanol, Molecular dynamics simulationmuch more complicated than purely hydrophobic1 Introductionsystems by exerting electrostatic forces on water 27-291.Hydrophobic interactions playint role inBecause of the electrostatic forces, there is no strongmany physico-chemical processes, such as proteindewetting transition observed in the collapse of theBphC enzyme>. However, Berme et al.[133lfolding!, micelle formation/ 23, water permeation inmembrane channels 4. and separation of hydrophobicthe collapse of the melittin tetramer in water byparticles 6-8. In 1973, Stillinger F.H. '9 argued thatcomputer simulations and observed a marked waterwater molecules at ambient conditions did not wetdewetting transition inside a nanoscale channel of thehard wall, and formed a water-vapor interface near thetetramer with a channel size of up to two or threegroups studied this phenomenonwater-molecule diametersTheof small solute moleculusing computer simulations and theoretical analysis110-23I. It was found that large hydrophobic solutes oras denaturants and alcohols, may greatly affect theurfaces can cause reorganizations of water molecules,hydrophobic/hydrophilic interaction in aqueousand there is a nanoscale dewetting transition, when thesolutions, and thus may influence the thermal stabilithydrophobic interaction is extremely strong 24-26.Thisor solubility of proteins 52-34). The mechanism of howcosolvent molecules affect hydrophobic/hydrophilichappens when two nanoscale hydrophobic platesapproach each other and reach a critical distanceinteractions is a basic issue in the protein chemistrywhich is still large enough to accommodate several field, but remains a matter of some controversy/2, 35,layers of water molecules, so the water trappedThus, examining the impact of these solutes on thebetween the two hydrophobic surfaces evaporatesdewetting transition phenomenon can provide a newrspective regarding the microscopic mechaninIsmspontaneously in a very short period of time before thecollapse of the two plates. This transition occurring onIn order to study the influence of ethanola microscopic length scale is analogous to a first-ordermolecules on the melittin tetramer folding, weperformed molecuphase transition from liquid to vapor. Proteins are中国煤化 Tis on theCNMHGCorresponding author. E-mail address: wangchunlei@sinap acReceived date: 2012-02-25REN Xiuping ef al. Nuclear Science and Techniques 23(2012)252-256dewetting transition of the melittin tetramer immersed from the all-atom OPLS (optimized potentials forin pure water and aqueous ethanol solutions, and liciquid simulations)force field3 1, The rigid potentialfound marked dewetting transitions inside a nanoscale SPC/E (extended simple point charge) was used forchannel of the melittin tetramer in both systems. It was water1391. and the SETtle algorithm was used to keepalso found that the ethanol molecules promoted thethe O-H distance fixed at 0.I nm and the H-o-Hdewetting transition. The vapor phase is preferred angle at 109.47o4o The GROMACS 4II MD packagebecause ethanol molecules locate at the liquid-vapor was used for all simulations with a time step of I fsnterface, and decrease the liquid-vapor surface energyGeometric combining rules were applied to calculateWe believe that the findings will be of help for the Lennard-Jones interactions between differentunderstanding the dewetting behavior of the mixed particles: Ei(eEu)and oi (0o)", where e and oisolution in the nanoscale space, including that in the are the parameters of atom () for the Lennard-Jonesnano-devices and biosystemsdiameter and well depth, respectively. The systemswere run at a constant pressure and temperature(NPT)2 Simulation methodof 10 Pa and 298 K for 5 ns, after the energyProtein melittin with a 26-residue polypeptide is aminimization with a steepest-descent algorithm. Themall toxic protein in honeybee venom, and ofteNPT ensemble was maintained at 298 K by the Noseself-assembles into a tetramer, as shown in Fig. 1. TheHoover thermostat and 10 Pa by the Parrinello-starting structure of the melittin tetramer was takenRahman barostat -. The Particle-Mesh Ewaldfrom the crystal structure deposited in PDB37I.Themethod4 was used to treat long-range electrostatictwo dimers of the tetramer were separated by ainteractions , and van der Waals interactions weredistance D, ranging from 0.55 to 0.75 nm to create atreated with a cutoff distance of 1. 20 nm. The 3-nsnanoscale channel, and were solvated in pure water orsimulations were carried out for each separation with8% aqueous ethanol solution. The channel was filledthree different initial configurations at the constantwith water molecules or ethanol molecules. andtemperature and pressure using the same methodsprotein atoms were constrained with a harmonicmentioned above, to explore the critical distance forpotential with a force constant of 1000 kJ mol-nmdewetting Dc below which vapor is the stable phaseThe simulation process of the melittin tetramer was the3 Results and Discussionsame as the dewetting simulation used in the previouswork of Berme et alsn. Twenty CI counterions were Figure 2 shows snapshots from two ' dewettingadded to all solvated water or mixture boxes to make simulations with an initial separation distance of D-the system electrically neutral(Fig. 1)0.55 nm. One sees from Fig. 2a that water moleculesinside the gap of the melittin tetramer in pure water are工quickly expelled within about 100 ps. Then, a strong,cooperative water dewetting transition occurs insidethe nanoscale channel in a large enough size toaccommodate two or three layers of water moleculesThe entire dewetting process is about 300 ps, with aEthanol3代fluctuation for a short period before all the watermolecules inside the channel are expelled. In Fig 2b,”water molecules in the gap of melittin tetramer in theethanol solutions are expelled, too, but it is slowerthan that in pure water. The ethanol molecules enterFig. I Schematics of imulation system. Melittin tetramer, CIater and cthanol are shown as ribbons. and van derthe gap of the melittin tetramer first, and then arespheres, thin lines and thick bonds, respectively.expelled with the中国煤化工 aqueousParameters for ethanol molecules were taken ethanol solutions.CNMH Gansitionwhich takes about 500 ps.REN Xiuping ef al. /Nuclcar Science and Techniques 23(2012)252-256t=0 pst=300Fig 2 Snapshots of water molecules inside the gap of the melittin tetramer in pure water(a) and of water or ethanol molecules insidethe gap of the melittin tetramer in aqueous ethanol solutions(b). Only water and ethanol molecules near the center of the channel wereplotted. which was defined as the region with a spherical radius of I nm from the center of the enlarged tetramer. For clarity, themelittin tetramer, water and ethanol are shown as transparent gray ribbons, gray bonds, and van der Waals spheres, respectively0.550.6-0.650.7+0.75(b)0550.6-0650.70.75路弱称E1004的Time/nsFig 3 Time traces of the atom number inside the channel of melittin tetramer in pure water(a)and aqueous ethanol solution( b)withD=0.55,06,065,0.7and0.75mFigure 3 plots a few time traces of the atom molecules inside the channel of the melittin tetramernumber inside the channel of the melittin tetramer, keeps almost equal to that with the wet initialstarting from different initial distances with one initial conditions, and the liquid phase is dominant. Theconfiguration. Fig 3a shows the results in pure water: simulation results show that the critical distance forat D-0.5 and 0.55 nm, water molecules inside the dewetting Dc in pure water is about 0.6 nm, which ischannel of the melittin tetramer are expelled and the equivalent to two water-molecule diameters. Fig 3bvapor phase is dominant; at D-0.6 nm, both the liquid shows the resul中国煤化工ions: waterphase and vapor phase exist inside the channel of the and ethanol moCNMH Gel of themelittin tetramer; at D>0.6 nm, the number of water melittin tetramer are expelled at D<0.65 nm, and theREN Xiuping ef al. /Nuclear Science and Techniques 23(2012)252-25655vapor phase is dominant; the number of water and D=0.55 nm, water inside the channel of melittinethanol inside the channel of the melittin tetramer atd tetramer are expelled very quickly, with only a small>0.7 nm keeps about equal to that with the wet initial fluctuation in water number, while the number of innerconditions, and the liquid phase is dominant; the ethanol increase with a large fluctuation. The liquidchannel of the melittin tetramer vacillates between the phase is dominant at D=0. 75 nm, both water andliquid phase and vapor phase at D-065 or 0. 7 nm. The ethanol have a large fluctuation. From Fig 4b, it couldsimulation results show that the critical distance for be deduced that ethanol preferentially locate in thedewetting Dc in aqueous ethanol solutions is 0.65-0.7 vicinity of the melittin tetramer. That is to say, ethanolnm, which is larger than that in pure water. Comparing molecules prefer to stay at the interfaces. Vazquez et aiFig 3b with Fig 3a, one finds that the melittin tetramermeasured the surface tension of aqueous alcoholcollapses more easily in aqueous ethanol solutions at solutions at the liquid-vapor interface and found thatlow ethanol concentration, We note that there are surface tension decreases as the ethanol concentrationmany atoms inside the channel of the melittin tetramer increases for a given temperature. It can be concludedin aqueous ethanol solutions than that in pure water.that the ethanol molecules locate at the liquid-vaporinterface, and decrease the liquid-vapor surface energy065through the previous results 45,46.Then, the vaporphase is preferred in the gap of the melittin tetramer,and the critical distance for dewetting becomes larger4 ConclusionsThe dewetting transition of the melittin tetramerimmersed in 8% aqueous ethanol solutions was包ahinvestigated by the molecular dynamics simulationsThe obvious dewetting transitions happen inside aTime/nsnanoscale channel of the melittin tetramer in pure055065407water and aqueous ethanol solution. The dewettingprocess is slightly faster in pure water(300 ps)thanin aqueous ethanol solution(500 ps). But the additionof ethanol molecules increases the critical distance fordewetting from 0.6 nm to 0.65-0.7 nm, and promotesthis dewetting transition. Also, the ethanol moleculesATpreferentially locate in the vicinity of the melittintetramer. It could be concluded that the ethanolmolecules locate at the liquid-vapor interface and1.0decrease the liquid-vapor surface energy. Therefore,ig. 4 Time traces of the atom number of water(a)and ethanol the vapor phase is preferred in the gap of the melittin(b)inside the channel of melittin tetramer in aqueous ethanolsolutions with D=0.55. 0.65 and 0.75 nmtetramer, and the critical distance for dewettingbecomes larger. This observation is helpful toTo explore mechanisms of the promoting effect understanding the dewetting behavior of the cosolventof ethanol on the dewetting transition . we calculatedsolutionsthe time traces of the atom number of water andethanol inside the channel of melittin tetramer in Acknowledgmentsaqueous ethanol solutions with D=0.55 nm(in vaporphase), 0.65 nm(vacillating between two phases)andWe thank ProfessorsFang, Jun Hu, and Bin0.75 nm(in liquid phase), respectively(Fig 4).AsLi, and Dr. Wenpe中国煤化工gzuo,formentioned above, the vapor phase is dominant attheir helpful sugYHaCNMHGas partly256REN Xiuping et al. /Nuclear Science and Techniques 23(2012)252-256supported by the National Science Foundation of 24 Lum K, Chandler D, Weeks J D J Phys Chem B, 1999China(No.10975175,90923002,2107322)and103:4570457Chinese Academy of Sciences(No. KJCX2-EW-N03). 25 ten Wolde P R, Chandler D. Proc Natl Acad Sci U SA,References2002,99:6539654326 Huang X, Margulis C J, Berme B J. 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