NUCLEIC ACID SSTRUCTURES, PROPERTIES, AND FUNCTION S

Victor A. Bloomfiel d

Donald M. Crothers

Ignacio Tinoco, Jr .

A. . .Preface i x

CHAPTER 1 INTRODUCTION 11. Biological Roles of the Nucleic Acids 12. Physical Chemistry and Nucleic Acid Function 2

3. Outline of this Book 3

4. Obtaining Nucleic Acids for Physical Chemical Study 6

5. The Periodical Literature of Nucleic Acids 7

6. Books and Monographs 8

7. Computer Analysis of Sequences and Structures 1 0

References 1 0

CHAPTER 2 BASES, NUCLEOSIDES, AND NUCLEOTIDES 1 3

1. Structures 1 32. Electron Distributions 2 23. Base Pairing and Base Stacking 3 1

References 4 1

CHAPTER 3 CHEMICAL AND ENZYMATIC METHODS 4 51. Introduction 4 5

2. Synthesis and Hydrolysis 46

3. Determination of Sequence 5 2

4. Determination of Secondary Structure 5 8

5. Determination of Tertiary Structure 69

References 7 2

CHAPTER 4 NUCLEIC ACID STRUCTURES FROM DIFFRACTION METHODS 7 9

1. Introduction 7 9

2. Diffraction Methods 8 0

3. General Features of Duplex DNA and RNA Structure 8 7

4. Detailed Structure and Sequence Dependence of Double-Stranded DNA 9 35. Double-Helical RNA Duplex 10 06. DNA Helices with Imperfect Base Pairing 10 17. Local Mobility of Double Helical Nucleic Acids 102

8. Transfer RNA 103

References 10 8

CHAPTER 5 STRUCTURE AND DYNAMICS BY NMR 11 1

1. Introduction to NMR Methods 11 22. Systematic Assignment of Resonances 12 2

3. Parameters for Structure Analysis 13 44. Characterization of Structures 14 15. Dynamic Analysis 14 66. Examples of NMR Studies of Nucleic Acids 15 07. Conclusions 158

References 158

CHAPTER 6 ELECTRONIC AND VIBRATIONAL SPECTROSCOPY 16 51. Electronic Absorption Spectra in the Ultraviolet 16 62. Fluorescence and Phosphorescence 18 13. Circular Dichroism 18 54. Linear Dichroism 19 95. Infrared Absorption and Raman Scattering 207 ,x.

References 21 7

CHAPTER 7 THEORETICAL METHODS 22 31.Theoretical Foundations 22 32. Simulation Methods 23 03. Theoretical Rationale for Conformational Preferences of Nucleic Acid Components 23 94. Sequence-Dependent Effects within Helices 24 25. Mismatches, Damaged DNA, and DNA-Drug Interactions 24 96. Concluding Perspectives 25 3References 254

CHAPTER 8 CONFORMATIONAL CHANGES 25 91. Single-Strand Stacking 26 12. Double Helix Formation by Oligonucleotides without Loops 27 13. Double Helix Formation by Oligonucleotides with Loops 29 14. Double Helix Formation with Polynucleotides 30 25. Environmental Effects on Helix Stability 30 76. Triple Helixes 31 07. G-Quartets 31 18. Predicting Secondary Structure 31 29. Predicting Three-Dimensional Structure 31 5

10. Helix-Helix Transitions 31 7

Appendix 31 7References 32 1

CHAPTER 9 SIZE AND SHAPE OF NUCLEIC ACIDS IN SOLUTION 33 51. Characterization at the Macromolecular Level 3362. Models for Molecular Structure 33 73. Frictional Coefficients for Model Shapes 34 14. Electrophoresis 34 55. Sedimentation Velocity 35 46. Diffusion 3607. Sedimentation Equilibrium 3648. Viscosity 3689. Viscoelasticity 369

10. Rotational Dynamics 37211. Scattering 38 112. Dynamic Light Scattering 39 013. Microscopy : Visualization of Single Molecules 39 614. Bending and Twisting of DNA 40 7

References 43 3

CHAPTER 1 0 SUPERCOILED DNA 44 3

1. Introduction 44 32. Topoisomerases and Gyrases 4443. Geometry and Topology of DNA Supercoiling 44 64. Energetics of Twisting and Bending 463

n5 . Stress-Induced Reactions 466

EReferences 47 0

CHAPTER 11 INTERACTION OF NUCLEIC ACIDS AND WATER AND IONS 475

1. Hydration 476 .2. Polyelectrolyte Behavior 48 83. Hydration in Ionic Solutions 504

f ;?

4. Specific Binding of Metal Ions and Polyamines 50 7

5. Mixed Aqueous-Nonaqueous Solvents 52 1

Appendix 522References 52 8

CHAPTER 1 2 INTERACTION AND REACTION WITH DRUGS 535

1. Modes of Interaction : Intercalation and Groove Binding 53 6

2. Theoretical Description of Binding Equilibria 53 7

3. Experimental Studies of Binding Equilibria 54 7

4. Solution Studies of the Structure of Drug-DNA Complexes 56 5

5. Kinetics of Ligand Binding 57 1

6. Natural Products that React Covalently with DNA 57 57 .Synthetic DNA Binding Agents 58 5

References 59 1

CHAPTER 1 3 PROTEIN-NUCLEIC ACID INTERACTIONS 59 7

1. Biological Role of Protein-Nucleic Acid Interactions 59 82. Elementary Energetics and Specificity of Interaction 60 13. DNA Sequence Motifs 61 54. Twisting and Bending of DNA Sequences in Protein Complexes 62 6

5. Looping of DNA Sequences 64 16. Structural Motifs in Sequence Specific DNA-Protein Interactions 64 5

7. Motifs in RNA-Protein Interactions 67 78. Structural Motifs in Enzymes that Act on Nucleic Acids 68 3

9. Solution Characterization of Binding Interactions 69 2

10. Kinetics and the Search Mechanism 70 4

References 71 1

CHAPTER ~ 4 HIGHER ORDER STRUCTURE 72 51. DNA Condensation in Vitro 725

2. DNA Packaging in Bacteriophage and Bacteria 749

3. DNA Packaging in Eukaryotes 75 6

References 76 6

Index 775