博碩士論文 104230002 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:5 、訪客IP:75.101.220.230
姓名 孫成瑜(Cheng-Yu Sun)  查詢紙本館藏   畢業系所 生物物理研究所
論文名稱 Ligand binding and activation of coupled receptor units
(Ligand binding and activation of coupled receptor units)
相關論文
★ 鍺銻碲相變化奈米薄膜之奈米尺度光熱性質的研究★ 波在一維系統中的傳播與局域化
★ 生物膜黏著引發的相分離—等效膜勢與數值模擬★ 非平衡生物膜上的區塊形成
★ 液滴上的彈性網絡★ 受體配體叢集在外力下的理論研究
★ 兩板間黏著叢集的強度★ 粒子黏著於生物膜所引發的細胞攝入作用之物理研究
★ 黏著叢集在時變外力下的強度★ 滲透壓對單層巨型微胞的影響
★ 模擬被clathrin蛋白質覆蓋的板塊狀胞吞作用★ T細胞受體活化反應之模型
★ Modeling geometrical trajectories of actin-based motility★ 隨機布耳網路在多連線且臨界情形下的特性
★ 模擬脂質雙層膜上的分子機器★ 組織動力學之建模
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   [檢視]  [下載]
  1. 本電子論文使用權限為同意立即開放。
  2. 已達開放權限電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。
  3. 請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。

摘要(中) 受體檢測外部刺激並作出適當反應的能力對於生物適應環境變化是相當必要的。許多理論模型都指出,受體單元之間的合作現象(cooperativity)在信號檢測中扮演著舉足輕重的角色。在本篇論文中,我們的理論將解釋受體間的交互作用是如何影響他們最外界刺激的反應與靈敏度(sensitivity)。首先,我們建構一個多單元受體(或N個耦合的一單元受體)的一般模型,其各單元間可以發生交互作用。透過這個模型,系統的能量得以確立,至於各微觀狀態的躍遷率之間的關係則依照細節平衡推導之。接下來,受體的平衡態分佈顯示,通過構象或鄰近單元對配體之親和力的耦合可以提高整個系統的靈敏度。前者使系統表現出類似MWC模型的行為;後者則對應Pauling模型。當外界環境具有高濃度的配體時,比起吻合Pauling模型的受體,類MWC模型的受體表現出更高的受體活化率。緊接著,我們使用Gillespie 演算法模擬受體的動力學。在受體的時間演化中,選擇被活化或是鍵結配體的路徑與各狀態所對應的能量有密不可分的關係。例如:高濃度配體下的活化與鍵結路徑不同於低配體濃度下的路徑。另一方面,隨著耦合強度增加和配體濃度降低,一個受體從沒有被活化且無鍵結配體的狀態演化至被活化同時鍵結著配體平均需要的時間也隨之增加。從定量的結果來看,我們發現高靈敏度且反應快速的受體可以通過其亞基之間的適度耦合來實現。最後,我們發現在平均場理論理一個含有許多單元的受體,一如我們預期,在單元間耦合強度超過一臨界值時,其受體活化率與配體濃度之間的關係如相變般產生出不連續的變化
摘要(英) The ability of a receptor to detect external stimuli and make appropriate responses is necessary for organisms to adapt environmental changes. It has been proposed in many models that cooperativity between receptors plays an important role in signal detection. In this thesis we present our theoretical investigation for the effects of interactions between the receptors on their response and sensitivity. First of all, we build a general model for a multi-unit receptor (or N coupled single-unit receptors) whose units interact with each other. The energy landscape is established and the transition rates between microstates are related to each other by the law of detailed balance. Next, equilibrium distributions of the receptor show that the sensitivity of the system can be improved by couplings through conformation or ligand binding affinity of nearby units. The former leads to behavior similar to the celebrated MWC model; the latter corresponds to Pauling model. The MWC-like receptor have higher activation level than Pauling receptor at high ligand concentration. Then we use Gillespie algorithm to simulate receptor dynamics. The kinetic pathway during receptor binding and activation depends strongly on the energy landscape. For example the kinetic pathways at high ligand concentration is different from that at low ligand concentration. On the other hand, the average time for a free, inactivate receptor to evolve to a fully bound and active state increases as the coupling increases and the ligand concentration decreases. Finally, we show that for a receptor with N >> 1 units, mean field analysis predicts a discontinuous jump in receptor activity under a change of ligand concentration. From our quantitative results, we find that a receptor with high sensitivity and rapid response can be achieved by moderate couplings between its subunits.
關鍵字(中) ★ 受體 關鍵字(英) ★ Receptor
論文目次 Contents
1 Introduction 1
1.1 Biologicalbackground.............................. 1
1.2 Motivation..................................... 3
2 Model 5
2.1 ASingle-unitreceptor.............................. 5
2.2 Amulti-unitreceptor............................... 8
2.3 SummaryofChapter2.............................. 9
3 Results 11
3.1 Equilibriumpropertiesofthesystem...................... 11
3.1.1 Asingle-unitreceptor.......................... 11
3.1.2 Atwo-unitreceptor........................... 14
3.2 Thedynamicsofthesystem........................... 17
3.2.1 GillespieAlgorithm............................ 17
3.2.2 Thekineticpathway........................... 18
3.2.3 Themeancompletiontime....................... 25
3.3 SummaryofChapter3.............................. 29
4 Meanfieldmodel 31
4.1 Meanfieldapproximation............................ 31
4.2 Result....................................... 32
4.3 DiscussionofChapter4............................. 33
5 Conclusion 37
Bibliography 39
II
參考文獻 Bibliography
[1] AntheaMaton.HumanBiologyandHealth., PearsonPrenticeHall, (1993).
[2] Alan Fersht.Structureandmechanisminproteinscience:aguidetoenzymecatalysis
and proteinfolding., W. H.Freeman, (2010).
[3] Bertil Hille.IonChannelsofExcitableMembranes., Sinauer Associates,Inc., (2001).
[4] Daniel Koshland,GeorgeNémethy,andDavidFilmer.Comparisonofexperimental
binding dataandtheoreticalmodelsinproteinscontainingsubunits., Biochemistry 5,
365. (1966).
[5] Daniel Gillespie.Ageneralmethodfornumericallysimulatingthestochastictimeevo-
lution ofcoupledchemicalreactions., Journal ofComputationalPhysics. 22, 403(1976).
[6] FelixHoppe-Seyler.Überdieoxydationimlebendenblute., Medchem Unt:133(1866).
[7] FriedrichHünefeld.DerChemismusinderthierischenOrganisation., Brockhaus, (1840).
[8] Hans Kessel.NelsonChemistry12., Nelson ThomsonLearning, (2003).
[9] HowardBerg.E.Coliinmotion., Springer-VerlagNewYork,(2004).
[10] Jacques Monod,JeanChangeux,andFrançoisJacobAllostericproteinsandcellular
controlsystems., J. Mol.Bol., 5306(1963).
[11] Jacque Monod,JeffriesWyman,JeanChangeux.Onthenatureofallosterictransitions:
A plausiblemodel., J. Mol.Bol.,12, 88(1965).
[12] John Hall,TextbookofMedicalPhysiology. Philadelphia., 930–937 (2016).
[13] KiyohiroImai.TheMonod-Wyman-Changeuxallostericmodeldescribeshaemoglobin
oxygenationwithonlyoneadjustableparameter., J. Mol.Bol., 167,741(1983).
[14] Kuo-Chen Chou.Low-frequencyresonanceandcooperativityofhemoglobin., Trends
BiochemSci., PMID2763333(1989).
[15] Max Perutz.Structureofhaemoglobin:athree-dimensionalFouriersynthesisat5.5-A.
resolution, obtainedbyX-rayanalysis., Nature,185 416(1960).
[16] Mihaela MihailescuandIrinaRussu.AsignatureoftheT ! R transitioninhuman
hemoglobin., Proc.Natl.Acad.Sci.,USA, 3773 (2001).
[17] Rob Phillips,JaneKondev,JulieTheriot.Physicalbiologyofthecell,2nded., Gerland
Scence, 274(2008).
[18] Sarah Marzen,HernanGarcia,andRobPhiliips.StatisticalmechanicsofMonod-
Wyman-Changeuxmodels., J. Mol.Bol., 425,1433(2013).
[19] Thomas DukeandDennisBray.Heightenedsensitivityofalatticeofmembranerecep-
tors., Proc.Natl.Acad.Sci.,USA,96, 10104.(1999).
[20] Thomas Duke,NicolasNovèreandDennisBray.ConformationalSpreadinaRingof
Proteins: AStochasticApproachtoAllostery., J. Mol.Bol., 5(2001).
[21] Uri Alon.IntroductiontoSystemsBiology., Chapman andHall (2006).
[22] William Press.NumericalRecipes3rded., Cambridge UniversityPress, (2007).
[23] YuhaiTu,ThomasShimizu,andHowardBerg.Modelingthechemotacticresponseof
Escherichiacolitotime-varyingstimuli., Proc.Natl.Acad.Sci.,USA, 105, 14855(2008).
指導教授 陳宣毅(Hsuan-Yi Chen) 審核日期 2018-1-16
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明