兰州大学机构库 >生命科学学院
Opiorphin溶液构象的初步分析
Alternative TitleSolution conformation of Opiorphin
达文平
Thesis Advisor董守良
2008-05-16
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
KeywordOpiorphin 溶液构象 核磁共振 分子动力学
AbstractOpiorphin (Gln-Arg-Phe-Ser-Arg-OH) 是一种在人唾液中分离得到的短肽分子,它能够通过在抑制两种锌金属肽链外切酶—中性肽链内切酶 (NEP) 和氨肽酶N (APN) 对脑啡肽等内源性阿片肽的降解,增强它们的生物活性,如镇痛、抗抑郁等。大鼠实验表明它的镇痛作用是吗啡的6倍。 本文的主要工作是通过2D-NMR的方法和分子动力学方法研究Opiorphin的空间构象。用固相合成的方法合成了Opiorphin。利用1H化学位移、主链的3<上标!>JNα偶合常数和质子间的NOE分析了Opiorphin中可能存在的二级结构。从结果来看,在DMSO-d6溶液中Opiorphin呈无规则卷曲状态。我们又用分子动力学计算方法模拟了Opiorphin在水溶液的构象,结果表明Opiorphin在水溶液中也呈柔性无规则卷曲状态,此构象可能是Opiorphin与其受体结合前的一种状态, 而柔性无规卷曲是两者正确结合的前提条件。 第一章主要介绍了核磁共振技术在生物大分子研究中的应用,包括基本知识、标记技术的发展、TROSY技术的发展、蛋白拼接、固体高分辨核磁共振、低温探头的应用、核磁共振联用技术(LC-NMR)以及核磁共振在医学上的应用。 第二章介绍了Opiorphin的研究背景和立题依据。主要介绍了锌金属肽酶及其抑制剂,Opiorphin等天然抑制剂的研究概况。通过对NMR方法的实验条件和图谱解析方法的概述说明了本文的立题依据。 第三章介绍了Opiorphin的固相合成以及NMR实验,通过二维图谱完成了对Opiorphin自旋系统的识别和顺序识别,并通过NOE,偶合常数法和化学位移指数法证明了Opiorphin在DMSO-d6溶液中呈柔性的无规则卷曲状态。 第四章介绍了用GROMACS模拟了Opiorphin在水溶液中可构象,通过能量最小化、限制性运动和分子动力学计算得到了稳定的构象。通过对其空间构象的分析发现在水溶液中Opiorphin也是以柔性的无规则卷曲状态存在的。 第五章是对本论文的研究总结,说明了本论文研究的主要结论和研究的不足之处与进一步工作的展望。
Other AbstractOpiorphin (Gln-Arg-Phe-Ser-Arg-OH) is a new small peptide isolated from human saliva. It potentates bioactivities of endogenous opioid peptides by inhibiting two enkephalin-inactivating zinc ectopeptidases, neutral ecto-endopeptidase (NEP) and ecto-aminopeptidase (APN), such as painkilling, antidepressant and so on. It is up to six times more potent than morphine in rat. This work studied the structure of Opiorphin using nuclear magnetic resonance spectroscopy and molecular dynamics. Opiorphin was synthesized by solid phase peptide synthesis. After analysis of the chemical shifts of 1H, 3JNα and NOE, we conclude that Opiorphin exist mainly as random coil in DMSO-d6. We also simulated the conformation of Opiorphin in water used the molecular dynamics computational method, the results suggested that Opiorphin exist mainly as flexible random coil in water too. This conformation may be the fit one before docking to its receptor, and maybe this random coil is suitable for their connection. Chapter I reviews basic knowledge of NMR and recent progresses in biomolecular NMR, which include TROSY experiments, proteinsplice, solid NMR, cryoprobe, LC-NMR and the applications of NMR in medicine. Chapter II provides the background of Opiorphin and the summary of this study. The zinc metallopeptidases and some nature inhibitor of zinc metallopeptidases, Opiorphin, were introduced, as well as the method of NMR in studying peptide. Chapter III introduces the solid phase synthesis of Opiorphin and NMR experiments. The sequence-specific assignment of spin systems and the complete assignment of proton resonances for backbone and side chain were introduced. Using NOE, 3JNα and CSI analyzing suggests that Opiorphin exist mainly as random coil in DMSO-d6. Chapter IV introduces the molecular dynamics study of Opiorphin by GROMACS. Several stable conformations after energy minimization (EM), position restrained (Pr) and molecular dynamics (MD) were obtained. Analysis of the molecular conformation suggests that Opiorphin exist mainly as random coil in water. Chapter V provides the summary of this study, including the conclusion and deficiencies.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221908
Collection生命科学学院
Recommended Citation
GB/T 7714
达文平. Opiorphin溶液构象的初步分析[D]. 兰州. 兰州大学,2008.
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