Binding constraint的問題，透過圖書和論文來找解法和答案更準確安心。 我們找到下列免費下載的地點或者是各式教學

布里斯洛中間體自由基反應機制之理論研究

為了解決Binding constraint的問題，作者謝明修 這樣論述：

含氮雜環卡賓（N-heterocyclic carbene）催化之化學反應中，布里斯洛中間體（Breslow intermediate）扮演重要的催化角色。布里斯洛中間體能以親核基（nucleophile）或自由基（radical）之形式參與反應。本論文探討布里斯洛中間體之自由基特性及形成機制（mechanism），其自由基可從氫自由基轉移或直接氧化形成。安息香縮合反應（benzoin condensation）中，布里斯洛中間體將氫原子轉移至苯甲醛（benzaldehyde）以形成自由基，此自由基可結合形成安息香產物，或排除反應之副產物，使其重新進入催化反應。唯此路徑之反應能障高於傳統非自

由基路徑。此研究亦探討四種布里斯洛中間體之不同電子組態的位能面。其中烯醇鹽（enolate）形式能產生偶極束縛態（dipole-bound state），此為產生自由基之新路徑；拉電子基（electron-withdrawing group）以及立體障礙基（bulky groups）可穩定基態。另外，我們亦研究布里斯洛中間體之碎片化（fragmentation）與重組（rearrangement）。布里斯洛中間體之催化反應可能因其碳氮鍵斷裂而中止，形成碎片。我們證實其反應中可以形成自由基，亦可形成離子。反應趨向之路徑與布里斯洛中間體之羥基的質子化型態有關。碎片化反應亦可視為轉酮醇酶（tran

sketolase）中之噻胺（thiamin）催化反應中之副反應；此研究證實轉酮醇酶透過限制布里斯洛中間體之結構與質子化型態，使其碳氮鍵斷裂需更高之反應能量，進而抑制此副反應。

以結構力學統計學習闡明蛋白質功能性質的分子機制

為了解決Binding constraint的問題，作者尼克森 這樣論述：

摘要. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiTable of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiiList of Figure

s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viList of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.1 Research problems . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Roles of backbone and side chains in protein folding and function . . . . . . . 31.3 Overview of molecular dynamics simulation . . . . . . . . . . . . . . . . . . . 41.3.1 Basic Theory . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . 41.3.2 Inter-atomic potentials . . . . . . . . . . . . . . . . . . . . . . . . . . 61.4 Coarse-grained approaches of protein simulation . . . . . . . . . . . . . . . . 71.5 Network analysis of proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 81.5.1 Elastic Network Models (

ENM) . . . . . . . . . . . . . . . . . . . . . 81.5.2 Graph theory to analyze protein structural network . . . . . . . . . . . 91.5.3 Allosteric regulation mechanisms through network based approaches . 101.6 The protein model systems under investigation . . . . . . . . . . . . . . . . . 121.6.1 Seri

ne protease: rat trypsin . . . . . . . . . . . . . . . . . . . . . . . . 131.6.2 PDZ3 domain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131.7 Outline of research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 Computational Methods . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . 162.1 All-atom molecular dynamic simulations . . . . . . . . . . . . . . . . . . . . . 162.2 Parameterization of bsENM by structure-mechanics statistical learning . . . . . 172.2.1 Atomic-to-CG mapping . . . . . . . . . . . . . . . . . . . . . . . . . 172.2.2 Compu

ting spring constants using fluctuation matching . . . . . . . . . 182.2.3 Determination of optimal lc cutoff . . . . . . . . . . . . . . . . . . . . 192.3 Construction of inter-residue rigidity graphs from statistically learned springconstants . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 202.4 Similarity analysis of rigidity graphs . . . . . . . . . . . . . . . . . . . . . . . 212.5 Protein rigidity graphs – statistical analysis . . . . . . . . . . . . . . . . . . . 222.5.1 Analysis of the statistical fluctuations of rigidity graph through theirmean-modes . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . 222.5.2 Calculation of mean-mode contents in an analysis time window . . . . 232.5.3 Identification of prominent eigenmodes of a rigidity graph . . . . . . . 242.6 Calculation of the residue rigidity scores for backbone and side-chains of themode

l proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252.7 Determination of prominent mechanical responses upon substrate binding/dissociationin the model proteins . . . . . . . . . . . . . . . . . . . . . . . . . . 262.8 Multiple sequence alignment for PDZ3 . . . . . . . .

. . . . . . . . . . . . . . 263 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283.1 How does the protein mechanical coupling network differ from the structuraltopology? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293.1.1 The co

llective modes of Laplacian matrices are related to skeleton springs 303.1.2 Non-skeleton springs ofKreveal chemically specific patterns in the proteinmechanical coupling network . . . . . . . . . . . . . . . . . . . . 303.1.3 Protein mechanical coupling network is sparse . . . . . . . . . . . . . 3

13.2 Protein mechanical couplings have heavy-tailed and scale-free network properties 323.2.1 The mechanical coupling networks in rat trypsin . . . . . . . . . . . . 333.2.2 The mechanical coupling networks in PDZ3 domain . . . . . . . . . . 343.3 Backbone and side-chain couplings exhibit different

patterns in their mechanicalhotspots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353.3.1 Mechanical hotspots of backbone-backbone couplings primarily locatein β-strands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363.3.2 Mechanical hotspots of side

-chain-side-chain couplings are different frombackbone-backbone couplings . . . . . . . . . . . . . . . . . . . . . . 373.3.3 Mechanical hotspots of backbone-side-chain have scattered couplings . 383.4 Emergence of long-range mechanical couplings from the prominent modes inrigidity graphs . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393.5 Residue rigidity scores defined for backbone and side-chain mechanical couplings– a useful metric for biological functions . . . . . . . . . . . . . . . . . 413.6 Mechanical relay in rat trypsin due to unbinding of BPTI . . . . . . .

. . . . . 433.6.1 The mechanical relay in catalytic domain rearrangement . . . . . . . . 453.6.2 The mechanical relay leads to collapse of calcium-binding loop . . . . 453.6.3 Dynamic allostery from the catalytic domain to the activation domain . 463.7 Mechanical relay in PDZ3 domain due to binding

of CRIPT peptide . . . . . . 473.7.1 Mechanical relay due to hydrogen bonding . . . . . . . . . . . . . . . 473.7.2 Mechanical relay of hydrophobic interactions spread across the β-sandwich 483.7.3 Hotspots in mechanical relay are mostly functional residues . . . . . . 483.7.4 MSA motivated by mecha

nical relay illustrates the evolutionary constraintsof inter-domain allostery . . . . . . . . . . . . . . . . . . . . . 494 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515 Figures and Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . 53Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89Appendix A 附錄標題. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109List of Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116