生物核磁共振波谱学
NMR in Biological Science
THNMR
YAN
Why learn NMR?
? 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
THNMR
YAN
1.1 A Remarkable Field
? Nobel Prize
? 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
THNMR
YAN
1.2 One of the two leading
technologies in structural biology
? Ref,Wuthrich K,Nature Structural Biology 5,492 - 495 (1998) THNMRYAN
1.2 One of the two leading
technologies in structural biology
PDB HOLDINGS (30-JUL-2001)
? Ref,PDB ANNUAL REPORT,July 2000 - June 2001
MO L E CU L E T Y PE
E X PE RE ME
N T A L
T E CH N IQ U
E
PRO T E IN S,P E PT ID E S,
A N D V IRU SE S
PRO T E IN / N U CL E IC
A CID CO MPL E X E S
N U CL E IC
A CID S
CA RBO H Y D
RA T E S
T O T A L
X-RA Y
DIF FRAC
TI ON
AND
OTHE R
1 1,63 0 556 580 14 1 2,78 0
NM R 1,91 8 73 383 4 2,37 8
THE OR ET
ICAL
MO D EL I N
G
288 19 23 0 330
T OT A L 1 3,83 6 648 986 18 1 5,48 8
THNMR
YAN
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).
THNMR
YAN
1.3 Great contributions to biology
? solution structures at atomic resolution in semi-
physiological conditions
? dynamic properties and the properties of partially
folded or unfolded proteins
? weak interactions between macromoloecules and
ligands
? a practical approach to drug design
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
THNMR
YAN
1.4 Milestones
? NMR
? 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
? X-ray
? 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
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
? PBD ANNUAL REPORT,2001
THNMR
YAN
1.4 Milestones
? X-ray,25 years older than NMR
? more order,more mature
? NMR,still in a developmental stage
? major improvements are still being made
? Incomplete view using only one single
techniques
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
THNMR
YAN
NMR Applications —— A-Z
? 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; THNMR
YAN
NMR Applications —— A-Z
? 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
THNMR
YAN
NMR Applications —— A-Z
? Structural Biology; Solid-state NMR
? Tertiary structure; Toxicology
? Ultrafast kinetics
? Visualization
? Water
? Xe-NMR
? Yielding
? Zoology
THNMR
YAN
Big Science NMR
? Numbers of NMR research groups
? newly established NMR centers
? wide applications
? automation
? a young emerging field of research
THNMR
YAN
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
THNMR
YAN
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)
THNMR
YAN
相关课程
生物系课程
? 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
? 有机化合物结构鉴定与有机波谱学
? 分析化学THNMRYAN
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!
THNMR
YAN
课 程 要 求
? 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
? SeminaTHNMR
YAN
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 NMRTHNMR
YAN
Seminar专题要求
? 从所列题目中选择或者自选，自选的要与教师商量
? 题目在第 3周（ 3月 14日）课上交给老师
? 主要文献应在 1997年以后
? 至少采用一篇综述性文献
? 2人一组，每组报告时间 7分钟，讨论 5分钟
? 提前 3天交提纲
? 需要用多媒体的提前 1天拷贝一下文件
THNMR
YAN
参考书目
? 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
? ftp://glove.2y.net
THNMR
YAN
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,S?rensen,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)
THNMR
YAN
- J,N,S,Evans "Biomolecular NMR Spectroscopy",Oxford University Press 1995,ISBN 0-
198-54766-8 (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)
THNMR
YAN
Journals
THNMR
YAN
Magnetic Resonance Journals
General
?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)
?Magnetic Resonance Quarterly (Raven Press)
THNMR
YAN
Welcome to the exiting field of
Be patient!
The system is coming up……
THNMR
YAN
NMR in Biological Science
THNMR
YAN
Why learn NMR?
? 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
THNMR
YAN
1.1 A Remarkable Field
? Nobel Prize
? 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
THNMR
YAN
1.2 One of the two leading
technologies in structural biology
? Ref,Wuthrich K,Nature Structural Biology 5,492 - 495 (1998) THNMRYAN
1.2 One of the two leading
technologies in structural biology
PDB HOLDINGS (30-JUL-2001)
? Ref,PDB ANNUAL REPORT,July 2000 - June 2001
MO L E CU L E T Y PE
E X PE RE ME
N T A L
T E CH N IQ U
E
PRO T E IN S,P E PT ID E S,
A N D V IRU SE S
PRO T E IN / N U CL E IC
A CID CO MPL E X E S
N U CL E IC
A CID S
CA RBO H Y D
RA T E S
T O T A L
X-RA Y
DIF FRAC
TI ON
AND
OTHE R
1 1,63 0 556 580 14 1 2,78 0
NM R 1,91 8 73 383 4 2,37 8
THE OR ET
ICAL
MO D EL I N
G
288 19 23 0 330
T OT A L 1 3,83 6 648 986 18 1 5,48 8
THNMR
YAN
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).
THNMR
YAN
1.3 Great contributions to biology
? solution structures at atomic resolution in semi-
physiological conditions
? dynamic properties and the properties of partially
folded or unfolded proteins
? weak interactions between macromoloecules and
ligands
? a practical approach to drug design
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
THNMR
YAN
1.4 Milestones
? NMR
? 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
? X-ray
? 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
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
? PBD ANNUAL REPORT,2001
THNMR
YAN
1.4 Milestones
? X-ray,25 years older than NMR
? more order,more mature
? NMR,still in a developmental stage
? major improvements are still being made
? Incomplete view using only one single
techniques
? Ref,Wagner G,Nature Structural Biology,4,841-844 (1997)
THNMR
YAN
NMR Applications —— A-Z
? 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; THNMR
YAN
NMR Applications —— A-Z
? 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
THNMR
YAN
NMR Applications —— A-Z
? Structural Biology; Solid-state NMR
? Tertiary structure; Toxicology
? Ultrafast kinetics
? Visualization
? Water
? Xe-NMR
? Yielding
? Zoology
THNMR
YAN
Big Science NMR
? Numbers of NMR research groups
? newly established NMR centers
? wide applications
? automation
? a young emerging field of research
THNMR
YAN
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
THNMR
YAN
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)
THNMR
YAN
相关课程
生物系课程
? 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
? 有机化合物结构鉴定与有机波谱学
? 分析化学THNMRYAN
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!
THNMR
YAN
课 程 要 求
? 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
? SeminaTHNMR
YAN
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 NMRTHNMR
YAN
Seminar专题要求
? 从所列题目中选择或者自选，自选的要与教师商量
? 题目在第 3周（ 3月 14日）课上交给老师
? 主要文献应在 1997年以后
? 至少采用一篇综述性文献
? 2人一组，每组报告时间 7分钟，讨论 5分钟
? 提前 3天交提纲
? 需要用多媒体的提前 1天拷贝一下文件
THNMR
YAN
参考书目
? 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
? ftp://glove.2y.net
THNMR
YAN
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,S?rensen,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)
THNMR
YAN
- J,N,S,Evans "Biomolecular NMR Spectroscopy",Oxford University Press 1995,ISBN 0-
198-54766-8 (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)
THNMR
YAN
Journals
THNMR
YAN
Magnetic Resonance Journals
General
?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)
?Magnetic Resonance Quarterly (Raven Press)
THNMR
YAN
Welcome to the exiting field of
Be patient!
The system is coming up……
THNMR
YAN
