古细菌水通道蛋白AqpM四聚体在脂质双分子层的分子动力学模拟
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摘要
目的通过古细菌水通道蛋白AqpM的分子动力学模拟,为其结构及功能研究奠定基础。方法将AqpM四聚体嵌入在二硬脂酰基磷脂酰乙醇胺(POPE)脂质双分子层,并加入水模型(TIP3P),使之模拟水通道蛋白与脂质和水分子在真实环境中的相互作用。结果模拟过程中RMSD值在最后2.35ns的变化较小,表明蛋白和脂质达到最终结构的平衡。结论成功进行了AqpM脂质平衡系统的分子动力学模拟,并对AqpM通道的结构作了进一步研究,这对了解水通道蛋白结构及其功能具有重要意义。
Objective To ascertain the structure and function of AqpM through a molecular dynamics(MD)simulation. Methods A tetramer of AqpM was embedded in a POPE lipid bilayer,and a water model(TIP3P)was added to simulate interaction among the water channel protein,the lipid,and water molecules in a real environment. ResultsThe change in the RMSD in the final 2.35 ns of the simulation was relatively small,indicating that the protein and lipid reached a final structural balance. Conclusion An MD simulation of balancing of AqpM in a lipid bilayer has been successfully performed,and the structure of the AqpM channel has been studied further.These findings will greatly help to understand the structure and function of this aquaporin.
Objective To ascertain the structure and function of AqpM through a molecular dynamics(MD)simulation. Methods A tetramer of AqpM was embedded in a POPE lipid bilayer,and a water model(TIP3P)was added to simulate interaction among the water channel protein,the lipid,and water molecules in a real environment. ResultsThe change in the RMSD in the final 2.35 ns of the simulation was relatively small,indicating that the protein and lipid reached a final structural balance. Conclusion An MD simulation of balancing of AqpM in a lipid bilayer has been successfully performed,and the structure of the AqpM channel has been studied further.These findings will greatly help to understand the structure and function of this aquaporin.
引文
[1]Agre P.Aquaporin water channels(Nobel Lecture)[J].Angew Chem Int Ed Engl,2004,43(33):4278-90.
[2]Kwon TH,Nielsen J,Moller HB,et al.Aquaporins in the Kidney[J].Handb Exp Pharmacol,2009,190(190):95-132.
[3]King LS,Kozono D,Agre P.From structure to disease:the evolving tale of aquaporin biology[J].Nat Rev Molr Cell Biol,2004,5(9):687-98.
[4]赵文龙.膜蛋白研究的里程碑[J].科学通报,2004,49(5):40-8.
[5]Lee JK,Kozono D,Remis J,et al.Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A[J].Proc Natl Acad Sci USA,2005,102(52):18932-7.
[6]Capaccioli S,Ngai KL,Ancherbak S,et al.Evidence of coexistence of change of caged dynamics at T(g)and the dynamic transition at T(d)in solvated proteins[J].J Phys Chem B,2012,116(6):1745-57.
[7]Wong AKL,Goscinski AM.A VMD plugin for NAMD simulations on amazon EC2[J].Procedia Computer Science,2012,9(11):136-45.
[8]Kitazawa S,Kameda T,Yagiutsumi M,et al.Solution Structure of the Q41NVariant of Ubiquitin as a Model for the Alternatively Folded N2State of Ubiquitin[J].Biochemistry,2013,52(11):1874-85.
[9]石静,李晓霞,刘文志,等.Particle-Mesh-Ewald(PME)算法在GPU上的实现[C].中国化学会学术年会第14分会场.2012.
[10]Jung JS,Preston GM,Smith BL,et al.Molecular structure of the water channel through aquaporin CHIP.The hourglass model[J].J Biol Chem,1994,269(20):14648-54.
[11]Gomes D,Agasse A,Thiébaud P,et al.Aquaporins are multifunctional water and solute transporters highly divergent in living organisms[J].Biochim Et Biophys Acta,2009,1788(6):1213-28.
[12]Stroud RM,Savage D,Miercke LJ,et al.Selectivity and conductance among the glycerol and water conducting aquaporin family of channels[J].FEBS Letters,2003,555(1):79-84.
[13]Goneu T,Walz T.The structure of aquaporins[J].Q Rev Biophys,2006,39(4):361-96.
[14]Beitz E,Wu B,Holm LM,et al.Point mutations in the aromatic/arginine region in aquaporin 1allow passage of urea,glycerol,ammonia,and protons[J].Proc Nat Acad Sci USA,2006,103(2):269-74.
[15]Froger A,Thomas D,Delamarche C,et al.Prediction of functional residues in water channels and related proteins[J].Protein Sci,1998,7(6):1458-68.
[16]Lagrée V,Froger A,Deschamps S,et al.Switch from an aquaporin to a glycerol channel by two amino acids substitution[J].J Biol Chem,1999,274(11):6817-9.
[17]Savage DF,Egea PF,Roblescolmenares Y,et al.Architecture and selectivity in aquaporins:2.5?X-Ray structure of aquaporin Z[J].Plos Biol,2003,1(3):E72-E72.
[18]Studer J,Bartsch C,Haas C.Aquaporin-4polymorphisms and brain/body weight ratio in sudden infant death syndrome(SIDS)[J].Pediatr Res,2014,76(1):41-5.
[19]Lee JK,Khademi S,Harries W,et al.Water and glycerol permeation through the glycerol channel GlpF and the aquaporin family:GlpF and the aquaporin family[J].J Synchrotron Radiat,2004,11(1):86-8.
[20]Agre P,Bonhivers M,Borgnia MJ.The aquaporins,blueprints for cellular plumbing systems[J].J Biological Chem,1998,273(24):14659-62.
[21]Mathai JC,Bezanilla F.No facilitator required for membrane transport of hydrogen sulfide[J].Proc Nat Acad Sci USA,2009,106(39):16633-8.
[22]Meng XW,Huang JP.Enhanced permeation of single-file water molecules across a noncylindrical nanochannel[J].Phys Rev E Stat Nonlin Soft Matter Phys,2013,88(1):14104.
[23]Arayasecchi R,Garate JA,Holmes DS,et al.Molecular dynamics study of the archaeal aquaporin AqpM[J].BMC Genomics,2011,12(4):1-13.
[24]Yool AJ,Campbell EM.Structure,function and translational relevance of aquaporin dual water and ion channels[J].Mol Aspects Med,2012,33(5-6):553-61.
[2]Kwon TH,Nielsen J,Moller HB,et al.Aquaporins in the Kidney[J].Handb Exp Pharmacol,2009,190(190):95-132.
[3]King LS,Kozono D,Agre P.From structure to disease:the evolving tale of aquaporin biology[J].Nat Rev Molr Cell Biol,2004,5(9):687-98.
[4]赵文龙.膜蛋白研究的里程碑[J].科学通报,2004,49(5):40-8.
[5]Lee JK,Kozono D,Remis J,et al.Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A[J].Proc Natl Acad Sci USA,2005,102(52):18932-7.
[6]Capaccioli S,Ngai KL,Ancherbak S,et al.Evidence of coexistence of change of caged dynamics at T(g)and the dynamic transition at T(d)in solvated proteins[J].J Phys Chem B,2012,116(6):1745-57.
[7]Wong AKL,Goscinski AM.A VMD plugin for NAMD simulations on amazon EC2[J].Procedia Computer Science,2012,9(11):136-45.
[8]Kitazawa S,Kameda T,Yagiutsumi M,et al.Solution Structure of the Q41NVariant of Ubiquitin as a Model for the Alternatively Folded N2State of Ubiquitin[J].Biochemistry,2013,52(11):1874-85.
[9]石静,李晓霞,刘文志,等.Particle-Mesh-Ewald(PME)算法在GPU上的实现[C].中国化学会学术年会第14分会场.2012.
[10]Jung JS,Preston GM,Smith BL,et al.Molecular structure of the water channel through aquaporin CHIP.The hourglass model[J].J Biol Chem,1994,269(20):14648-54.
[11]Gomes D,Agasse A,Thiébaud P,et al.Aquaporins are multifunctional water and solute transporters highly divergent in living organisms[J].Biochim Et Biophys Acta,2009,1788(6):1213-28.
[12]Stroud RM,Savage D,Miercke LJ,et al.Selectivity and conductance among the glycerol and water conducting aquaporin family of channels[J].FEBS Letters,2003,555(1):79-84.
[13]Goneu T,Walz T.The structure of aquaporins[J].Q Rev Biophys,2006,39(4):361-96.
[14]Beitz E,Wu B,Holm LM,et al.Point mutations in the aromatic/arginine region in aquaporin 1allow passage of urea,glycerol,ammonia,and protons[J].Proc Nat Acad Sci USA,2006,103(2):269-74.
[15]Froger A,Thomas D,Delamarche C,et al.Prediction of functional residues in water channels and related proteins[J].Protein Sci,1998,7(6):1458-68.
[16]Lagrée V,Froger A,Deschamps S,et al.Switch from an aquaporin to a glycerol channel by two amino acids substitution[J].J Biol Chem,1999,274(11):6817-9.
[17]Savage DF,Egea PF,Roblescolmenares Y,et al.Architecture and selectivity in aquaporins:2.5?X-Ray structure of aquaporin Z[J].Plos Biol,2003,1(3):E72-E72.
[18]Studer J,Bartsch C,Haas C.Aquaporin-4polymorphisms and brain/body weight ratio in sudden infant death syndrome(SIDS)[J].Pediatr Res,2014,76(1):41-5.
[19]Lee JK,Khademi S,Harries W,et al.Water and glycerol permeation through the glycerol channel GlpF and the aquaporin family:GlpF and the aquaporin family[J].J Synchrotron Radiat,2004,11(1):86-8.
[20]Agre P,Bonhivers M,Borgnia MJ.The aquaporins,blueprints for cellular plumbing systems[J].J Biological Chem,1998,273(24):14659-62.
[21]Mathai JC,Bezanilla F.No facilitator required for membrane transport of hydrogen sulfide[J].Proc Nat Acad Sci USA,2009,106(39):16633-8.
[22]Meng XW,Huang JP.Enhanced permeation of single-file water molecules across a noncylindrical nanochannel[J].Phys Rev E Stat Nonlin Soft Matter Phys,2013,88(1):14104.
[23]Arayasecchi R,Garate JA,Holmes DS,et al.Molecular dynamics study of the archaeal aquaporin AqpM[J].BMC Genomics,2011,12(4):1-13.
[24]Yool AJ,Campbell EM.Structure,function and translational relevance of aquaporin dual water and ion channels[J].Mol Aspects Med,2012,33(5-6):553-61.