现化专题-孔老师课件2结构生物学导论

1、ProteinProtein变换变换FreeinductionFreeinductiondecay1D11D1Hspectrumof2D2DMoleculardynamicsMoleculardynamicsTheNobelPrize inTheNobelPrize inChemistryMartinMichaelArieh定义分子动力学模拟定义分子动力学模拟生命体所做的每件事情都可以理解为原子的振动-Forcee4pppxpForcee4pppxpbpy ean）Ex bngdvopd1kb(diE)=ii21+ii2k+is6dmdm1qi +2+2nonnnucleiiandj.The4

2、.1EneyeFromspecctroscopy,IR,s= 1kb(diii2= 1k(iii2k+4.1EneyeFromspecctroscopy,IR,s= 1kb(diii2= 1k(iii2k+ikiDihedralFromquantumchemistry,6 m dm v= Vander=6EquaoFi=gradFi=EquaoFi=gradFi=E +dEupdateviatt+t/2 updateriatt+ t goto1.= Fi= )nuon.dndhqunvbnsbt -t=10-15huhyhn能能垒和时间能能垒和时间尺1kcal/mol ps,5kcal/mol

3、 ns,10kcal/mol s以能能垒=0exp(G/kBT)，其中0=10-12水通道的计水通道的计算机模B.L.deGrootandH.Grubmuller(2001)Science 294, 2353-2357.Tajkhorshid,andSchulten,K.(2002)Sciencelitetobaccolitetobacco100万个原子，模拟时长50ns，10000个P.L.Freddolino,andK.Schulten,Structure,14:437-449,应用应用获得体系的动力学性质（dynamicsandProteinProteinpurifiedfromJohn

4、ProteinProteinpurifiedfromJohnKendrew Showeda75%-helical-155aminoacids,17ProteinProteinTwocopieseachof& chains of myoglobin in a SolvedbyMaxStructureHemeFeis 6-FourNofhemeOneNfromproximalOnefromStructureHemeFeis 6-FourNofhemeOneNfromproximalOnefromH2OorsobindCooperativeHemoglobinoxygenStartbindingwi

5、thgivenCooperativeHemoglobinoxygenStartbindingwithgivenaffinityinsSubsequentbindingOnlyitivecooperativeAdvantage:bindingismoresensitivesmallchangesinligandDeoxy=Tense(T)(nooxygenOxy=Relaxed(R)(oxygenSignalStructuralSignalStructuralbasisofproteinkinasesandprotein-蛋白激蛋白激酶A（PKA)的晶体结胰岛素胰岛素受体激酶的结受体酪氨酸激酶（

6、受体酪氨酸激酶（RTK）的自我调化受体酪氨酸受体酪氨酸激酶的自我调C-Src激酶C-Src激酶的自抑C-Src活性位点C-Src活性位点的重C-Src激酶C-Src激酶的活钾离子通钾离子通Bertil钾离子通道的3钾离子通道的3Highrate:107-108 K+ ions/s Gating:conductionisturnedonandclosingayopeningpictureofpictureofatetramericK+ channelmadeofporeselectivityCrystalstructureofCrystalstructureofRoderickDoyleetal

7、.Science,280:69-77AK+AK+ channelmimicsthehydrationsurroundingaK+ TwospecificTwospecificconfigurationsofK+MechanismforMechanismforionK+ bindingK+ bindingsitesandG(K+Na+)=(Gpore(Na+)(Gpore(K+)能的贡献Noskovetal.Nature,431:830-834GGwith能的贡献Noskovetal.Nature,431:830-834GGwithLossinFullyflexible -FullyPartlyGating:theonsetandGating:theonsetanddurationoftheconductiveeWhatisthe