分子生物物理学

MolecularBiophysics分子生物物理学分子水平结构功能研究生物体系物理学性质、行为Biopolymers:Nucleicacid(DNA,RNA)ProteinMoleculesinBiosystemSaccharideLipidOtherPROTEINSTRUCTUREA链Gly.Tle.Val.Glu.Gln.Cys.Cys.Aln.Ser.Val.Cys.Ser.Leu.Tyr.Gln.Leu.Glu.Asn.Tyr.Cys.AsnOH12671120B链Phe.Val.Asn.Gln.His.Leu.Cys.Gly.Ser.His.Leu.Val.Glu.Ala.Leu.Tyr.Leu.Val.Cys.Gly.Glu.Arg.12719Gly.Phe.Phe.Tyr.Thr.Pro.Lys.AlaOH30牛胰岛素的化学结构S—SSSSS1965年中国在世界上首次用化学方法人工合成的蛋白质－牛胰岛素SecondaryStructurePrimaryStructureTertiaryStructuresupersecondaryStructureormotifdomainQuaternaryStructureHierarchyofProteinStructurebyLinderstrøm-LangChiralLalanineCOOHCH3NH2HPropertyofaminoacidzwitterionUnchargedstructureMinorcomponentDipolarion,orzwitterionMajorcomponentClassificatoryofaminoacidbasedsidechains(Rgroups)Non-polarG,A,V,L,I;F,W,P,M,PolarneutralS,T,N,QacidicD,E;C,YbasicR,K,H?HistidineProteinPrimaryStructurePeptidebondBackboneSidechainAmine/NterminusCarboxyl/CterminusPauling&CoreyC-N,0.149nmC=N,0.127nm=180=180=0=0?CCN,CCONHC3.20(3.0)2.80(2.70)2.90(2.80)2.40(2.20)O2.70(2.60)2.70(2.60)2.40(2.20)N2.70(2.60)2.40(2.20)H2.00(1.90)MinimalDistance(Å)betweennonbondingatom(G.N.Ramachandran)phi(),psi(Y),andomega(W)interactionRelationwithEnergyanddistancecharger-charger-1charger-dipoler-2dipole-dipoler-3charge-induceddipoler-4dipole-induceddipoler-6Transientdipole-induceddipoler-6RelationwithEnergyanddistance126rBrAEVanderWaalsforceLennard-Jonespotential10kJ·mol-1，range:0.3～0.5nmH-bonddefinition,H-bondlocationO….H-XHydrogenbondOHXHydrogenbondscanvaryinstrengthfromveryweak(1-2kJmol−1)toextremelystrong(40kJmol−1),sostrongastobeindistinguishablefromacovalentbond,asintheionHF2−.Typicalvaluesinclude:O—H...:N(7kcal/mol)O—H...:O(5kcal/mol)N—H...:N(3kcal/mol)N—H...:O(2kcal/mol)ProteinSecondaryStructure1951,PaulingPZ0=-57=-47p=0.54nmz0=0.15nmHelicesrepetitivesecondarystructureNCHelicesarethemostabundantformofsecondarystructurecontainingapproximately32-38%oftheresiduesinglobularproteins(KabschandSander,1983)a-helix310helixp-helixnrP3.613-57-473.60.1540.55310-49-263.00.2000.60p-57-74.40.1150.51Paral--119+1132.00.3200.64Antiparal--139+1352.00.3400.68Parametersofsecondarystructure[n]isthenumberofresiduesperhelicalturn[r]isthehelicalriseperresidue(nm)[p]isthehelicalpitch(nm).H-bondAtomsinH-bondloopradius3.613i,i+4132.3310i,i+3101.9pi,i+5162.8Parametersofsecondarystructurea-helixintroduction32-38%ofallresiduesinglobularproteinsTheaveragelengthofanalphahelixis10residues.Found(-64+/-7,-41+/-7)/ideal(-57.8,-47.0)Thestructurerepeatsitselfevery5.4Åalongthehelixaxis,i.e.wesaythatthea-helixhasapitchof5.4Å.a-heliceshave3.6aminoacidresiduesperturn,i.e.ahelix36aminoacidslongwouldform10turns.Theseparationofresiduesalongthehelixaxisis5.4/3.6or1.5Å,i.e.thea-helixhasariseperresidueof1.5Åthephiandpsianglesofthealphahelixlieinthecenterofanallowed,minimumenergyregionoftheRamachandran(phi,psi)map.Whyalpha-helixisabundantinnativeglobularprotein?thedipolesofhydrogenbondingbackboneatomsareinnearperfectalignment.theradius(2.3angstrom)ofthehelixallowsforfavorablevanderWaalsinteractionsacrossthehelicalaxissidechainsarewellstaggeredminimizingstericinterference•COgrouptowardcarboxylterminus•NHgrouptowardamideterminus•H-bond,i-(i+4)•Sidechain:i-(i+3);i-(i+4)•interactionsbetweeniandi+4stabilizehelixDistortionsofa-helicesThemajorityofa-helicesinglobularproteinsarecurvedordistortedsomewhatcomparedwiththestandardPauling-Coreymodel.Why?1.Thepackingofburiedhelicesagainstothersecondarystructureelementsinthecoreoftheprotein2.Prolineresiduesinducedistortionsofaround20degreesinthedirectionofthehelixaxis3.Solvent.Exposedhelicesareoftenbentawayfromthesolventregion.ThisisbecausetheexposedC=OgroupstendtopointtowardssolventtomaximisetheirH-bondingcapacity,i.e.tendtoformH-bondstosolventaswellasN-Hgroups.310helixintroductionOnly3.4%oftheresiduesareinvolvedin310helices,andnearlyallthoseinhelicalsegmentscontainingi-i+3hydrogenbonds.Ideal(-74.0,-4.0)/found(-71.0and-18.0)CO---HNhydrogenbond:i-i+3Standard310helixProlinehelixLefthandedhelix3.0residuesperturnpitch=9.4ÅNohydrogenbondinginthebackbonebuthelixstillforms.Poly-glycinealsoformsthistypeofhelixCollagen:highinGly-Proresidueshasthistypeofhelicalstructurep-helicesintroductionThepihelixisanextremelyraresecondarystructuralelementinproteins.thebackboneC=OofresidueihydrogenbondstothebackboneHNofresiduei+5.i--i+5H-bonds2.8angstrom1.thephiandpsianglesofthepurepihelix(-57.1,-69.7)lieattheveryedgeofanallowed,minimumenergyregionoftheRamachandran(phi,psi)map.2.thepihelixrequiresthattheangletau(N-Ca-C')belarger(114.9)thanthestandardtetrahedralangleof109.5degrees.3.thelargeradiusofthepihelixmeansthepolypeptidebackboneisnolongerinvanderWaalscontactacrossthehelicalaxisforminganaxialholetoosmallforsolventwatertofill.4.sidechainsaremorestaggeredthantheideal3.10helixbutnotaswellasthealphahelix.H-bond:1-5alpha-helix,surfaceofprotein,barrieramphiphilicproteindesignprojectsbyDegrado,USAHelicalwheeltoolsHelixdipoleThepartialchargesontheamidehydrogenandcarbonyloxygenareshowninunitsoftheelementarychargecontrib