人朊病毒蛋白及其突变体溶剂可及性和模拟分析.pdfVIP

维普资讯 第 l9卷 2期 叶]围 病 毒 学 l9 (2)：l58一 l62 2004年4月 VIR0L0GICA SINICA April 2004 人朊病毒蛋白及其突变体的溶剂可及性和模拟分析 孙桂鸿 1,27郭明雄 ，龚 睿 ，梅芳华 ，万云莲 ，肖庚富 ，田 (1．武汉大学生命科学学院．湖北武汉 430072；2．武汉大学医学院，湖北武汉 430071；3．湖北中医学院计算机室，湖北武汉 430061) SolventAccessibilityandComputerM odelingAnalysisontheNativeandthe M utantsofHumanPrionProtein SUN Gui—hong，．GUO M ing—xiong ，GONG Rui，MEIFang—hua，WAN Yun—lian3XIAO Geng—fu ，TIAN Bo ， f，．CollegeofLifeScience，WuhanUniversiyt,Wuhan430072，China,2．MedicalCollege，WuhanUniversity,Wuhan 430071，China；3．Compt~terRoom，HubeiCollegeD，TraditionalChineseMedicine，Wuhan430061，ChinaJ Abstract：Prions are unprecedented infectious pathogens thatcause a group of invariably fatal neurodegenerativediseasesby anentirely novelmechanism．Prion diseasesresultfrom abnormally folded isoform (PrPso)ofthecellularprionprotein (PrP)．In orderto investigatethemoleculra mechanismsoftheconversionofPrP intoPrP ．wecalculatedthesolventa‘ccessibilityofaminoacid residuesinnativeHuPrPanditssingleaminoacidresidualmutants，suchasM 166V,S170N，E200K and R220K．W ealsomodeledstructuraloverlapsofnativePrPand itsmutants，analyzedtheirrootmean squaredfRMS)deviations．Resultsshowedthatthelocalconformationisintenselydifferentbetweenthe nativePrPand itsmutantsowingtothevariationofM 166V etc．Thesingleami noacidresidualmutant notonlyleadtogreatchangesofthesolventaccessiblesurfaceraea (SASA)andpositionsofpart residues，butalso influencethedistributionoftheprotein surfacechrages．Thesechangesmayadapt wellto thelocalsurroundingsofthe secondary interactions．W e also concludethatthere issome difference