人胰岛淀粉样多肽hiapp单体及二聚体与对popg磷脂膜相互作用的分子动力学模拟分析-凝聚态物理专业毕业论文.pdf.docx

A B S T R A C T T he aggregatio n of h um an islet am y lo id po ly p eptide (h IA P P o r am y lin) is associated w ith the path o g enesis o f ty pe 2 d iabetes m e llitu s. In c reasin g ev idence su g gests th at th e in teractio n o f h IA P P w ith (3-ce ll m em b ran es p lay s a cru cial ro le in cytoto x icity. H ow ever, th e m o lecu lar m ech an ism o f interactio n and su b seq uent m em b ran e p erturbatio n at ato m ic lev e l rem ain s p o o rly u n d ersto o d . In th is stu d y, as a first step to u nd erstan d th e m echan ism o f h IA P P -ind uced cytoto x icity, w e hav e in vestigated th e d e ta ile d in te ra c tio n s o f h IA P P m o n o m e r a n d d im e r w ith a n io n ic palm ito y lo leo ly o p h o sp h atid y lg lycero l (P O P G ) b ilay er u sing all-ato m m o lecu lar d y n am ics (M D ) sim u latio n s. M u ltip le M D sim u latio n s h ave b een p erfo rm ed b y em p lo y in g the in itia l co n fig u ratio ns w h ere th e N -term inal reg ion o f h IA P P is p re-in serted in P O P G b ilayer. O u r sim u latio n s sh o w that electro static interactio n b etw een h IA P P an d P O P G b ilayer p lays a m ajo r ro le in peptid e-lip id interactio n . In p artic u lar, th e N -term in a l p o sitiv ely -ch arg ed resid u es L y s l an d A rg il m ak e a d om inant co ntrib utio n to the inte ractio n . D u rin g p eptid e-lip id interactio n p ro cess, peptid e d im erizatio n o ccu rs m o stly th ro ug h the C -term in al 2 0 -3 7 reg io n co nta in in g the am y lo id o g e n ic 2 0 -2 9 -resid u e segm en t. M em b ran e -b o u n d h IA P P d im ers d isp lay a pro n o un ced ab ility o f m em b rane perturb atio n than m o no m ers. T h e h ig her b ilay er p ertu rbatio n p ro p en sity o f h IA P P d im er lik ely resu lts fro m th e co o perativ ity o f th e peptide-peptid e interactio n (o