Download 生物核磁共振波谱学NMR in Biological Science 闫永彬博士Yong

生物核磁共振波谱学
NMR in Biological Science
闫永彬
博士
Yong-Bin YAN, Ph.D.
清华大学
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生物科学与技术系
Why learn NMR?
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A remarkable field
One of the two leading technologies in
structural biology
Great contributions to biology
A special window to the development of
modern structural biology and
biophysics
1.1 A Remarkable Field
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Nobel Prize
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1943年 O. Stern 物理学奖
— 测定质子磁矩
1944年 I. I. Rabi 物理学奖
— 测定磁矩的共振方法
1952年 F.Bloch & E. M. Prucell 物理学奖
— 发现核磁共振现象
1991年 R. R. Ernst 化学奖
— FT NMR & 2D NMR
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1.2 One of the two leading
technologies in structural biology
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1.2 One of the two leading
technologies in structural biology
PDB HOLDINGS (30-JUL-2001)
MOLECULE TYPE
EXPEREME
NTAL
TECHNIQU
E
X-RAY
DIFFRAC
TION
AND
OTHER
NMR
THEORET
ICAL
MODELIN
G
TOTAL
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PROTEINS, PEPTIDES,
AND VIRUSES
PROTEIN/NUCLEIC
ACID COMPLEXES
NUCLEIC
ACIDS
CARBOHYD
RATES
TOTAL
11,630
556
580
14
12,780
1,918
73
383
4
2,378
288
19
23
0
330
13,836
648
986
18
15,488
Ref: PDB ANNUAL REPORT, July 2000 - June 2001
Molecular weight distribution of the NMR structures
deposited in the Brookhaven PDB as of December
1997.
Guntert P. Q Rev
Biophys, 31:145-237
(1998).
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1.3 Great contributions to biology
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solution structures at atomic resolution in semiphysiological conditions
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dynamic properties and the properties of partially
folded or unfolded proteins
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weak interactions between macromoloecules and
ligands
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a practical approach to drug design
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Ref: Wagner G. Nature Structural Biology. 4: 841-844 (1997)
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1.4 Milestones
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NMR
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1946 - the first spectra of solid compounds
1957 - the first spectra of a protein - RNase A
1982 - the first protein spectra was assigned
1985 - the first solution structure of a protein
1997 - 924 NMR structures in PDB
Today - over 2,378 structures in PDB
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X-ray
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1913 - the first diffraction patterns of crystals were reported
1934 - the first protein crystallized and examined - pepsin
1960 - the first protein crystal structures - myoglobin, hemoglobin
1997 - 5012 crystals structures in PDB
Today - over 12,780 structures in PDB
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Ref: Wagner G. Nature Structural Biology. 4: 841-844 (1997)
PBD ANNUAL REPORT, 2001
1.4 Milestones
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X-ray: 25 years older than NMR
• more order, more mature
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NMR: still in a developmental stage
• major improvements are still being made
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Incomplete view using only one single
techniques
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Ref: Wagner G. Nature Structural Biology. 4: 841-844 (1997)
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NMR Applications —— A-Z
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Agriculture; Animal Behavior; Analytic Chemistry
Biomolecule NMR; Biophysics; Biotechnology
Chemistry; Cells; Clinical Medicine;
Dynamics; Drug design and drug discovery
Energy metabolism; Equilibrium-NMR studying
Folding; Flexibility; Flow-NMR
Graphics
Hydrogen-exchange; HPLC-NMR
Interactions; In Vivo Measurements; Imaging
J-coupling;
NMR Applications —— A-Z
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Kinetics
Lipids, Ligands Binding
Membrane proteins; Medicine; Micro-imaging;
Material Science
Na23-NMR
Oil detection
Protein structures; Partially structured proteins;
Pharmacokinetics; Physics; Physiology
Quantum computation
Recognition; RNA structures
NMR Applications —— A-Z
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Structural Biology; Solid-state NMR
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Tertiary structure; Toxicology
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Ultrafast kinetics
Visualization
Water
Xe-NMR
Yielding
Zoology
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Big Science NMR
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Numbers of NMR research groups
newly established NMR centers
wide applications
automation
a young emerging field of research
About this course——
What will be covered?
 Introduction to the principles of NMR
 Theory required for the understanding of
important experiments
 A selection of the most widely-used 2D NMR
techniques
 Interpretation of these spectra
 Applications of NMR in Biological Science
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and what not?
 quantum mechanical treatment of NMR
(although some equations will occur!!!)
 solid state NMR, MRI techniques
 working with NMR data bases
 empirical correlations for chemical
shifts (increment systems)
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相关课程
生物系课程
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生物物理
生物物理前沿
医学物理
Advance NMR Spectroscopy
(NMR Lab. 内部培训)
化学系课程
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有机化合物结构鉴定与有机波谱学
分析化学
What is required?
knowledge of 1D NMR, J coupling patterns, chemical
shift etc., e.g., Biophysics, Analytical chemistry
regular (!) attention of the course, since most
"individual sections" require an understanding of the
previous ones.
"re-reading"
(and "re-thinking"!) of the material
on a regular basis, and working out your own solutions to the
problems given in the course – to make sure that you have really
grasped the concepts and developed a working knowledge!
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课程要求
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掌握核磁共振技术的基本原理
熟悉核磁共振测量需要的样品要求
掌握核磁共振基本参数的含义,能够进行1D
NMR谱的解析
熟悉2D NMR谱的含义和获得的信息和解析方
法
了解蛋白质结构计算的步骤
了解NMR在生命科学中的主要应用
Semina
课程设置
周
次
第
2
周
第
3
周
第
4
周
第
5
周
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日 期
3月 7日
3 月 14 日
3 月 21 日
3 月 28 日
内
容
绪论
第一节 核磁共振基础（1）
学
时
1
2
第一节 核磁共振基础（2）
第二节 核磁共振一维谱（1）——1D 1H NMR
第二节 核磁共振一维谱（2）——1D 13C NMR 等
第三节 核磁共振二维谱（1）——基础
第三节 核磁共振二维谱（2）——常用二维谱
第四节 由 NMR 谱图进行蛋白质溶液结构计算介绍
第五节 NMR 在生物科学中的应用介绍(或 Seminar)
典型习题讲解和讨论/答疑
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Seminar专题
 Equilibrium NMR studies of unfolded and partially folded proteins
 Kinetic studies of protein folding using NMR spectroscopy
 Hydrogen Exchange in proteins using NMR
 Nucleic acids structure
 X-ray crystallography and NMR
 Nucleic acids structure
 NMR structures of large proteins and protein complexes
 Protein-DNA interactions from NMR
 In vivo NMR studies
 structure-based drug design from NMR
 Protein dynamics from NMR
 NMR and membrane proteins
 Paramagnetic NMR
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Seminar专题要求
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从所列题目中选择或者自选，自选的要与教师商量
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题目在第3周（3月14日）课上交给老师
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主要文献应在1997年以后
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至少采用一篇综述性文献
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2人一组，每组报告时间7分钟，讨论5分钟
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提前3天交提纲
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需要用多媒体的提前1天拷贝一下文件
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参考书目
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宁永成.《有机化合物结构鉴定与有机波谱学》，清华大学出
版社，第一，第二版
夏佑林.《生物大分子多维核磁共振》，中国科技大学出版社
Wüthrich K. NMR of Proteins and Nucleic Acids. New York: John
Wiley and Sons, 1986
周海梦等，《生物物理》中核磁共振部分
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ftp://glove.2y.net
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Some literature recommendations
Monographs
- A.Abragam "The principles of Nuclear Magnetism", Oxford University Press, 1978 (6.
Auflage),ISBN 0-198-51236-9.
(physics, very gut & very difficult to understand, the "old testament" of NMR)
- R. R. Ernst, G. Bodenhausen, A. Wokaun "Principles of NMR in One and Two Dimensions",
Oxford Science Publ. 1987, ISBN 0-198-55647-0.
(physical chemistry, very exact & very difficult, the "new testament")
- O. W. Sørensen, G. W. Eich, M. H. Levitt, G. Bodenhausen, R. R. Ernst, Progr. NMR Spectrosc.
16, 163-192 (1983).
(the original article about product operators, but very readable! – if you skip some paragraphs)
- R. K. Harris "Nuclear Magnetic Resonance Spectroscopy, A Physicochemical View", Longman
Scientific & Technical 1986, ISBN 0-582-44653-8.
(easily readable introduction to basic concepts, no modern techniques)
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- J. N. S. Evans "Biomolecular NMR Spectroscopy", Oxford University Press 1995, ISBN 0198-54766-8 (QP519.9.N83E94 1995).
(stress on biomolecular NMR, incl. proteins & nucleic acids, but also including a compact, yet
concise introduction, nice book, reasonably priced)
- H. Kessler, M. Gehrke, C. Griesinger, Angew. Chem. Int. Edn. Engl. 1988, 27, 490-536.
( good review on all 2D techniques, incl. product operator explanation, still up to date)
- W. R. Croasmun, W. M. K. Carlson, ed. "Two-Dimensional NMR Spectroscopy; Applications
for Chemists and Biochemists", VCH 1994, ISBN 1-56081-664-3 (QD/96/N8/T87/1987).
(mixture of introductory and application chapters, on heteronuclear spectroscopy etc.,
expensive)
- D. Shaw, "Fourier Transform NMR Spectroscopy", Elsevier Scientific Publishing Co., New
York, 1976 (Res. QC/762/S45/2/1984).
(good on principle and features of FT, otherwise outdated)
- J. K. M. Sanders, B. K. Hunter, "Modern NMR Spectroscopy, A Guide for Chemists", Oxford
University Press, 2nd ed. 1993 (QD/96/N8/S25).
(no product operator description, but very good description of applications for 2D
techniques,incl. example spectra).
- J. Cavanagh, W.J. Fairbrother, A. G> Palmer III, N. J. Skelton, "Protein NMR Spectroscopy,
Principles and Practice", Academic Press, San Diego 1996, ISBN 0-12-164490-1
(QP551.P69726 1995)
(Lots of theory, quantum-mechanics & product operators, FT, relaxation measurements,
despitetitle large section on 2D methods)
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Journals
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Magnetic Resonance Journals
General
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•Journal of Magnetic Resonance (Academic Press)
Specialized
•J. Biomolecular NMR, Ed. K. Wuthrich, (published by Kluwer Academic Publishers).
•Solid State Nuclear Magnetic Resonance (published by Elsevier Science )
•Journal of Magnetic Resonance Imaging
•Magnetic Resonance in Medicine
•Magnetic Resonance Imaging (Elsevier)
•Magnetic Resonance in Chemistry (John Wiley & Sons)
•Magnetic Properties and Magnetic Resonance
•NMR in Biomedicine (John Wiley & Sons)
•Quarterly of Magnetic Resonance in Biology and Medicine (Mediamix)
Educational
Concepts in Magnetic Resonance
Applied and Review
•Annual Reports on NMR Spectroscopy (Academic Press)
•Applied Magnetic Resonance (Springer)
•Progress in Nuclear Magnetic Resonance Spectroscopy (published by Elsevier Science )
•Bulletin of Magnetic Resonance (Journal of the International Society of Magnetic Resonance)
•Magnetic Resonance Materials in Physics, Biology and Medicine
•Magnetic Resonance Review (Gordon & Breach Publishers)
•NMR: Basic Principles and Progress. NMR: Grundlagen und Fortschritte (Springer-Verlag)
Welcome to the exiting field of
Be patient!
The system is coming up……
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