泵浦糖蛋白底物选择非特异性的物理模型

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1、内蒙古大学硕士学位论文substrateswithintracellulartargetsispHdependent．CleanermodelexplainssomeofP—gP’Ssubstratesarepumpedoutofcellsdirectly．Bothmodelsabovedon’tconsideraboutP—gP’Sportalsenough．Flippasemodelconsiderstheportalsandexplainsnon．specificityofP—gP’Ssubstratesandthedifferentialha

2、ndlingofitssubstratesbasedontheirlipidsolubilitysuccessfully．However,flippasemodelcan’texplainthreeproblems：(1)theinfluenceofionicstrengthonP—gP’Sdimension(2)themainreasonofsubstratesenteringthelumenofP—gPefficiently(3)theconsumptionnumberofATPhydrolyzedpersubstratetransported．

3、Tosolvethethreeproblemsofflippasemodel，fromthepointofviewthatthebasicinteractionbetweenbiologicalmoleculesiselectricandthechangeoffreeenergydecidesthedirectionandlimitofanreaction，theelectrostaticfreeenergyofP—gPandthesystemP—gp---substratearecalculatedbasedonDebye—Hfickeltheor

4、y．Somesignificantresultsareobtained．Thethesisisdividedintothreechapters．Inchapter1，P—gP’Sstructure，substrates’patterns，mechanismofpumpingaction，theroleofanti—apoptosis，P—gPinhibitorsandexperimentalmethodsareintroduced，whichprovidethebasisofthesimplifiedmodelofP—gP’Spumpingactio

5、n．Inchapter2，thebackground，applicationandderivationofDebye—Hfickeltheoryareintroduced，whicharethetheoreticalbasisofthecalculationofelectrostaticfreeenergy．Chapter3isthemainpartofthispaper．AsimplifiedmodelofP—gP’Spumpingactionandequivalentdistributionofchargeareobtained．Aformula

6、oftheelectrostaticfreeenergyofP—gPwithoutsubstratesisinduced，whichdescribestheinfluenceofionicstrengthandP—gP’SdimensionontheelectrostaticfreeenergyofP-gP．Furthermore，thechangeofelectrostaticfreeenergyIV内蒙古大学硕士学位论文isalsoinducedintheprocessofsubstratesenteringthelumenofP—gP．Them

7、ainreasonofsubstratesenteringthelumenofP—gPwithahigheffectivenessisproposed．Theenergyminimumoftransportingasubstrateisobtained，whichhasthesameorderastheenergyfromoneATPhydrolyzed．ItisillustratedthatoneK鼹needstobehydrolyzedpersubstratetransported．Twoindirectwaysareproposedtoinhi

8、bitP一辨．KEYWORDS：Pump-．glycoprotein；Mechanismofpumpinga