現(xiàn)化專題-孔老師課件2結(jié)構(gòu)生物學(xué)導(dǎo)論

1、ProteinProtein變換變換FreeinductionFreeinductiondecay1D11D1Hspectrumof2D2DMoleculardynamicsMoleculardynamicsTheNobelPrize inTheNobelPrize inChemistryMartinMichaelArieh定義分子動力學(xué)模擬定義分子動力學(xué)模擬生命體所做的每件事情都可以理解為原子的振動-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能能壘和時間能能壘和時間尺1kcal/mol ps,5kcal/mol

3、 ns,10kcal/mol s以能能壘=0exp(G/kBT)，其中0=10-12水通道的計水通道的計算機模B.L.deGrootandH.Grubmuller(2001)Science 294, 2353-2357.Tajkhorshid,andSchulten,K.(2002)Sciencelitetobaccolitetobacco100萬個原子，模擬時長50ns，10000個P.L.Freddolino,andK.Schulten,Structure,14:437-449,應(yīng)用應(yīng)用獲得體系的動力學(xué)性質(zhì)（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)的晶體結(jié)胰島素胰島素受體激酶的結(jié)受體酪氨酸激酶（

6、受體酪氨酸激酶（RTK）的自我調(diào)化受體酪氨酸受體酪氨酸激酶的自我調(diào)C-Src激酶C-Src激酶的自抑C-Src活性位點C-Src活性位點的重C-Src激酶C-Src激酶的活鉀離子通鉀離子通Bertil鉀離子通道的3鉀離子通道的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+)能的貢獻Noskovetal.Nature,431:830-834GGwith能的貢獻Noskovetal.Nature,431:830-834GGwithLossinFullyflexible -FullyPartlyGating:theonsetandGating:theonsetanddurationoftheconductiveeWhatisthe