AssociateInvestigator,NIBS,Beijing,ChinaPhone：010-80726688-8570
Fax：010-80726689
E-mail：huangniu@nibs.ac.cn
教育经历Education:1994南开大学物理系生物物理学学士学位
BachelorofBiophysics，DepartmentofPhysicsUniversityofNankai,Tianjin,
2003马里兰大学巴尔的摩分校药学博士学位
Ph.D.，DepartmentofPharmaceuticalSciences，UniversityofMarylandatBaltimore
工作经历ProfessionalExperience:Oct.2007-北京生命科学研究所高级研究员
AssistantInvestigator,NIBS
Dec.03-Oct.2007加利福尼亚大学旧金山分校制药化学和生物制药学系博士后
Postdoctoralassociate,Depts.ofPharmaceuticalChemistryandBiopharmaceuticalSciences,UniversityofCaliforniaatSanFrancisco
Sep.94-Aug.98中国医学科学院&中国协和医科大学药物研究所研究助理
Researchassistant，InstituteofMateriaMedica,PekingUnionofMedicalCollege&ChineseAcademyofMedicalSciences
研究概述：近年来，生物学领域的研究进展极大地加深了我们对和疾病密切相关的分子靶标的认识。然而，如何有效地利用这些生物学信息，进而针对疾病靶标来设计治疗性药物，还需要我们从原子水平上来掌握生物大分子的三维结构和生物功能之间的关系。我们将进一步开发基于物理学原理的计算化学理论和分子模拟技术，来研究在分子识别过程（蛋白－蛋白，蛋白－核酸和蛋白－配体相互作用）中的自由能和空间构象的变化，从而指导蛋白质结构和功能的改造，以及加速新药的设计与开发。我们将充分利用本实验室在大分子模拟和小分子设计方面的条件和经验，积极促进物理和计算科学在生物学中的应用，同时探索高性能科学计算（High-performanceComputing,HPC）的方法学研究。http://www.huanglab.org.cn主要研究方向一．改进分子对接技术和提高打分函数的精度在已知受体结构和作用位点的情况下，分子对接技术（MolecularDocking）可被用于自动匹配受体结合腔穴和数据库中的小分子化合物，并预测与受体结合作用最强的一组化合物，来进行活性测试以节省新型先导化合物开发的周期和成本。我们将系统地研究和改进目前计算受体和配体结合自由能方法中的局限性因素，例如诱导契合、去溶剂化效应、熵效应，以及静电作用的精确计算等，来提高虚拟筛选的成功率。二．研究可被配体调控的蛋白－蛋白相互作用蛋白－蛋白相互作用（Protein-ProteinInteractions,PPIs）在许多生物学过程中起关键性作用。然而，基于这类重要分子靶标开发小分子药物的成功率非常低。我们认为其中的一个重要原因是PPIs的成药性（Druggability）与其结构的内在柔性密切相关，因此我们将利用多种构象搜寻手段来模拟PPIs界面的动态构象变化以及相关的自由能变化，预测可能的小分子结合腔穴，并且定量分析和评估这些结合位点的成药性，从而为下一步的虚拟筛选奠定基础。ResearchDescription:Theopeningofthe21stcenturyhasmarkedwiththesequencingofthehumangenome.Today,theunderstandingofthesequenceandstructureofbiologicallyrelevanttargetsisgrowingrapidlyandresearchersfrommanydisciplines,physicsandcomputationalscienceinparticular,aremakingsignificantcontributionstomodernbiologyanddrugdiscovery.State-of-the-artcomputationalchemistryandmolecularmodelingtechniquescanbeappliedtostudyawiderangeofchemicalandbiologicalsystemsofinterest,whichenableustoacquireinformationnotobtainablebyexperimentaltechniques,toinvestigatestructuralphenomenaattheatomiclevelandtoidentifynovelcompoundswithdesiredbiologicalcharacteristics.Ourlaboratoryisinterestedindevelopingandapplyingcomputationaltechniquestostudythestructuralandenergeticbasisofmolecularrecognition(i.e.,protein-protein,protein-DNAandprotein-ligandinteractions).Asidefromitsfundamentalbiologicalinterest,suchtheoreticalstudieshavetremendouspracticalvaluesofwhichoneofthemostimportantisstructure-baseddrugdesign.Publications1.XiaoboWan,YueMa,ChristopherL.McClendon,LilyJun-shenHuangandNiuHuang.AbInitioModelingandExperimentalAssessmentofJanusKinase2(JAK2)Kinase-PseudokinaseComplexStructure.PLoSComp.Biol.2013,Inpress.2.FanqiZeng,ShimingPeng,LiLi,LibingMu,ZhenghuaZhang,ZhiyuanZhangandNiuHuang.HAToff:structure-basedidentificationofdrug-likeinhibitorsofp300histoneacetyltransferase.ActaPharmaceuticaSinica.2013,Inpress.3.XiaoboWan,WeiZhang,LiLi,YutingXie,WeiLiandNiuHuang.ANewTargetforAnOldDrug:IdentifyingMitoxantroneasaNanomolarInhibitorofPIM1KinaseviaKinome-wideSelectivityModeling.J.Med.Chem.2013,Feb26.[Epubaheadofprint]4.YaoWu,XiaodongDai,NiuHuangandLifengZhao.Apartitionfunction-basedweightingschemeinforcefieldparameterdevelopmentusingabinitiocalculationresultsinglobalconfigurationalspace.J.Comp.Chem.2013,Feb19.[Epubaheadofprint]5.YanliWang,MinyuLiu,RanCao,MingYin,RiuhuaXiaoQuanhaiLiuandNiuHuang.ASolubleBis-chelatedGold(I)DiphosphineCompoundwithStrongAnticancerActivityandLowToxicity.J.Med.Chem.2013,Jan30.[Epubaheadofprint]6.YaoQ,CuiJ,WangJ,LiT,WanX,LuoT,GongYN,XuY,HuangN,ShaoF.StructuralmechanismofubiquitinandNEDD8deamidationcatalyzedbybacterialeffectorsthatinducemacrophage-specificapoptosis.ProcNatlAcadSciUSA.2012Nov21.[Epubaheadofprint]7.RanCao,MinyuLiu,MinYin,QuanhaiLiu,YanliWang,NiuHuang.DiscoveryofNovelTubulinInhibitorsviaStructure-BasedHierarchicalVirtualScreening.J.Chem.Inf.Model.2012.8.ShimingPeng,XingyuLin,ZongruGuo,NiuHuang.IdentifyingMultiple-TargetLigandsviaComputationalChemogenomicsApproaches.Curr.Top.Med.Chem.2012,12:1363-1375.9.XingyuLin,XipingHuang,GangChen,RyanWhaley,ShimingPeng,YanliWang,GuoliangZhang,ShaohuiWang,XiangWang,BrianRoth,NiuHuang.LifeBeyondKinases:Structure-BasedDiscoveryofSorafenibasNanomolarAntagonistof5-HTReceptors.J.Med.Chem.2012,55:5749-59.(SelectedbyF1000Pharmacology&DrugDiscovery,CongreveM:2012.http://f1000.com/717951322).10.AndrewChristoffersonandNiuHuang.HowtoBenchmarkMethodsforStructure-BasedVirtualScreeningofLargeCompoundLibraries.MethodsinMolecularBiology.2012.819:187-95.Book11.LifengZhao,ChuanjieWuandNiuHuang.MutualSolubilitiesStudyforBinaryMixturesofDipropyleneGlycolDimethylEtherandWaterviaMolecularDynamicsSimulationandAMOEBAPolarizableForceField.Fluid.Phase.Equilib.2011,310:32-8.12.AndrewChristofferson,LifengZhao,HanziSun,ZhenHuangandNiuHuang.TheoreticalStudiesoftheBasePairFidelityofSelenium-modifiedDNA.J.Phys.ChemB.2011,115:10041-8.13.QiangPei,AndrewChristofferson,HuiZhang,JijieChai,NiuHuang,ComputationalInvestigationoftheEnzymaticMechanismsofPhosphothreonineLyase,BiophysicalChemistry.2011;157(1-3):16-23.14.NiuHuangandMatthewP.Jacobson.Binding-SiteAssessmentbyVirtualFragmentScreening.PLoSONE.2010,5:e1010915.JohnIrwin,BrianShoichet,MichaelMysinger,NiuHuang,FrancescoColizzi,PascalWassamandYiqunCao.Automateddockingscreens:afeasibilitystudy.J.Med.Chem.2009,52:5712-2016.ChayaS.Rapp,CherylSchonbrun,MatthewP.Jacobson,ChakrapaniKalyanaramanandNiuHuang.AutomatedSitePreparationinRescoringofReceptorLigandComplexes.Proteins.2009,77:52-6117.QingYao,JixinCui,YongqunZhu,GuolunWang,LiyanHu,ChengzuLong,RanCao,XinqiLiu,NiuHuang,SheChen,LipingLiuandFengShao.AbacterialtypeIIIeffectorfamilyusesthepapain-likehydrolyticactivitytoarrestthehostcellcycle.Proc.Natl.Acad.Sci.USA.2009,106:3716-372118.ZhiweiHuang,YingcaiFeng,XiaojingWu,XiaojunWang,XingguoXiao,WenhuiLi,NiuHuang,LichuanGu,GuangmingZhongandJijieChai.Structuralandbiochemicalmechanismsofthecatalysis,activationandinhibitionofCPAF(ChlamydialProtease/Proteasome-likeActivityFactor).CellHost&Microbe.2008,4:529-54219.NiuHuangandBrianShoichet.ExploringOrderedWatersinMolecularDocking.J.Med.Chem.2008,51:4862-4865.20.LinjieChen,HuayiWang,JieZhang,LichuanGu,NiuHuang,Jian-MinZhouandJijieChai.Structuralbasisforthecatalyticmechanismofphosphothreoninelyase.Nat.Struct.Mol.Biol.2008,15:101-10221.NiuHuangandMatthewP.Jacobson.Physics-basedMethodsforStudyingProtein-LigandInteractions.Curr.Opin.DrugDiscov.Devel.2007,10:325-331.22.NiuHuang,JohnIrwinandBrianShoichet.BenchmarkingSetsforMolecularDocking.J.Med.Chem.2006,49:6789-6801.23.NiuHuang,ChakrapaniKalyanaraman,KatarzynaBernackiandMatthewP.Jacobson.LigandBindingFree-energyCalculationsviaPhysics-basedScoringMethods.Phys.Chem.Chem.Phys.2006,8:5166-5177.24.NileshK.Banavali,NiuHuangandAlexanderD.MacKerell,Jr.ConservedPatternsinBackboneTorsionChangesAllowForSingleBaseFlippingfromDuplexDNAwithMinimalDistortionoftheDoubleHelix.J.Phys.Chem.B.2006,110:10997-11004.25.NiuHuang,ChakrapaniKalyanaraman,JohnIrwin,MatthewP.Jacobson.Physics-basedScoringofProtein-ligandComplexes:EnrichmentofknowninhibitorsinLarge-ScaleVirtualScreening.J.Chem.Inf.Model.2006,46:243-253.26.VictorM.Anisimov,GuillaumeLamoureux,IgorV.Vorobyov,NiuHuang,BenoitRoux,AlexanderD.MacKerell,Jr.DeterminationofElectrostaticParametersforapolarizableForceFieldBasedontheClassicalDrudeOscillator.J.Chem.Theory.Comp.2005,1:153-168.27.NiuHuangandAlexanderD.MacKerell,Jr.Specificityinprotein-DNAinteractions:Energeticrecognitionbythe(cytosine-C5)-methyltransferasefromHhaI.J.Mol.Biol.2005,345:265-274.28.JohnR.Horton,GaryRatner,NileshK.Banavali,NiuHuang,YongseokChoi,MartinA.Maier,VictorE.Marquez,AlexanderD.MacKerell,Jr.,XiaodongCheng.CaughtintheMiddleoftheAct:VisualizationofaPutativeTransitionStateDuringDNABaseFlipping.Nucl.Acids.Res.2004,32:3877-3886.29.NiuHuang,AshishNagarsekar,GuanjunXia,JunHayashiandAlexanderD.MacKerell,Jr.IdentificationofNon-Phosphate-ContainingSmallMolecularWeightInhibitorsoftheTyrosineKinasep56LckSH2DomainviainSilicoScreeningagainstthepY+3BindingSite.J.Med.Chem.2004,47:3502-3511.30.NiuHuangandAlexanderD.MacKerell,Jr.AtomisticviewofBaseflippinginDNA.Phil.Trans.Roy.Soc.Lond.SeriesA.2004,362:1-22.31.HuiPeng*,NiuHuang*,JingQi,PingXie,ChenXu,JianxiangWangandChunzhengYang.IdentificationofnovelinhibitorsofBCR-ABLtyrosinekinaseviavirtualscreening.Bioorg.Med.Chem.Lett.2003,13:3693-3699.*equalcontribution32.NiuHuang,NileshK.BanavaliandAlexanderD.MacKerell,Jr.Protein-facilitatedbaseflippinginDNAbycytosine-5-methyltransferase.PNAS,2003,100:68-73.33.YongpingPan,NiuHuang,SamChoandAlexanderD.MacKerell,Jr.ConsiderationofMolecularWeightDuringCompoundSelectioninVirtualTarget-BasedDatabaseScreening.J.Chem.Inf.Comput.Sci.2003,43:267-27234.NiuHuangandAlexanderD.MacKerell,Jr.AnAbInitioQuantumMechanicalStudyofHydrogen-BondedComplexesofBiologicalInterest.J.Phys.Chem.A,2002,106:7820-7827.35.NiuHuang,LinboQu,QiqingZhu,FengmingChu,GuangzhongYangandZongruGuo.StudiesontheStructure-ActivityRelationshipofRetinoids:MolecularModelingofInteractionbetweenSelectiveRetinoidsNuclearReceptors.ActaPharmaceuticaSinica.1999,34:358-36236.NiuHuang,FengminChuandZongruGuo.StudiesontheStructure-ActivityRelationshipofRetinoids:HanschAnalysisand3D-QSARStudiesonSpecificLigandsofRetinoidXReceptor.ActaPharmaceuticaSinica.1998,33:442-44837.QiqinZhu,ZongruGuo,NiuHuang,MinminWang,andFengmingChu.ComparativeMolecularFieldAnalysisofaSeriesofTaxolAnalogues.J.Med.Chem,1997,40:4319-432838.MinminWang,NiuHuang,GuangzhongYangandZongruGuo.StudiesontheStructure-ActivityRelationshipofRetinoids:II.3D-QSARofRetinoidsandReceptorInteraction.ActaPharmaceuticalSinica.1997,32:43-4839.NiuHuang,MinminWang,FengminChuandZongruGuo.StudiesontheStructure-ActivityRelationshipofRetinoids:I.3D-QSARofRetinoidalAnti-CarcinogenicActivities.ActaPharmaceuticaSinica.1996,31:932-939
