E-Book, Englisch, Band 2, 638 Seiten
Reihe: Challenges and Advances in Computational Chemistry and Physics
Sponer / Lankas / Šponer Computational studies of RNA and DNA
2006
ISBN: 978-1-4020-4851-7
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark
E-Book, Englisch, Band 2, 638 Seiten
Reihe: Challenges and Advances in Computational Chemistry and Physics
ISBN: 978-1-4020-4851-7
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark
This book integrates modern computational studies of nucleic acids, ranging from advanced electronic structure quantum chemical calculations through explicit solvent molecular dynamics (MD) simulations up to mesoscopic modelling, with the main focus given to the MD field. It gives an equal emphasis to the leading methods and applications while successes as well as pitfalls of the computational techniques are discussed.
Autoren/Hrsg.
Weitere Infos & Material
1;CONTENTS;6
2;PREFACE;9
3;Chapter 1 BASICS OF NUCLEIC ACID STRUCTURE;12
3.1;1. BACKGROUND;12
3.2;2. THE BUILDING BLOCKS;13
3.2.1;2.1 Chemical Composition;13
3.2.2;2.2 Structure;14
3.3;3. NUCLEIC ACID CONFORMATIONS;20
3.3.1;3.1 Double Helical Forms;22
3.3.2;3.2 Other Nucleic Acid Conformations;27
3.3.3;3.3 Nucleic Acids with Modified Components;28
3.3.4;3.4 Folded Single-Stranded Nucleic Acids;29
3.4;4. NUCLEIC ACIDS IN COMPLEXES;32
3.4.1;4.1 Recognition of Nucleic Acids by Small Molecules;34
3.4.2;4.2 Recognition Between Nucleic Acids and Proteins;36
3.5;5. WEB RESOURCES FOR NUCLEIC ACID STRUCTURES;42
3.5.1;5.1 The Primary Archives of Experimental Molecular Structures – PDB and NDB;43
3.5.2;5.2 Content of the NDB;44
3.5.3;5.3 Structural Classification of RNA (SCOR);45
3.6;ACKNOWLEDGEMENTS;45
3.7;REFERENCES;46
4;Chapter 2 USING AMBER TO SIMULATE DNA AND RNA;56
4.1;1. AMBER APPLIED TO NUCLEIC ACIDS;56
4.1.1;1.1 Setting up AMBER MD Simulations;57
4.1.2;1.2 AMBER Dynamics;58
4.1.3;1.3 AMBER Analysis;61
4.2;2. MOLECULAR DYNAMICS OF NUCLEIC ACIDS;67
4.3;3. CHALLENGES FOR THE FUTURE;74
4.4;ACKNOWLEDGEMENTS;75
4.5;REFERENCES;76
5;Chapter 3 THEORETICAL STUDIES OF NUCLEIC ACIDS AND NUCLEIC ACID-PROTEIN COMPLEXES USING CHARMM;83
5.1;1. INTRODUCTION;83
5.2;2. CHARMM AS A TOOL FOR MODELING STUDIES OF NUCLEIC ACIDS;85
5.3;3. CHARMM NUCLEIC ACID FORCE FIELDS;87
5.4;4. COMPUTATIONAL STUDIES OF SMALL NUCLEIC ACIDS AND RELATED COMPOUNDS;88
5.5;5. SIMULATIONS STUDIES OF OLIGONUCLEOTIDES;90
5.6;6. SIMULATION STUDIES OF PROTEIN NUCLEIC ACID COMPLEXES;93
5.7;7. SUMMARY;95
5.8;ACKNOWLEDGEMENTS;96
5.9;REFERENCES;96
6;Chapter 4 CONTINUUM SOLVENT MODELS TO STUDY THE STRUCTURE AND DYNAMICS OF NUCLEIC ACIDS AND COMPLEXES WITH LIGANDS;105
6.1;1. INTRODUCTION;106
6.2;2. COMPUTER SIMULATION OF NUCLEIC ACIDS USING CONTINUUM SOLVENT MODELS;107
6.2.1;2.1 Molecular Mechanics Force Fields to Study Biomolecular Structure and Dynamics;107
6.2.2;2.2 Continuum Solvent Modeling;108
6.2.3;2.3 Molecular Dynamic Simulation on Nucleic Acids Using Continuum Models;115
6.2.4;2.4 DNA and RNA as Drug Targets;117
6.2.5;2.5 Application of Continuum Solvent Models to Nucleic Acid Motif Structure Prediction;119
6.2.6;2.6 Docking of Ligands to Nucleic Acids;121
6.2.7;2.7 Conclusions and Outlook;123
6.3;ACKNOWLEDGEMENTS;124
6.4;REFERENCES;124
7;Chapter 5 DATA MINING OF MOLECULAR DYNAMIC TRAJECTORIES OF NUCLEIC ACIDS;130
7.1;1. INTRODUCTION;130
7.2;2. THE CLASSICAL APPROACH;131
7.2.1;2.1 Level of Representation;132
7.2.2;2.2 The Force Field;133
7.2.3;2.3 Simulation Methods;135
7.2.4;2.4 Analysis of MD Trajectories;136
7.3;3. CHALLENGES FOR THE FUTURE;150
7.3.1;3.1 Force-Field Refinement;150
7.3.2;3.2 Reactivity in Nucleic Acids;151
7.3.3;3.3 Complexes with Proteins;151
7.3.4;3.4 Unusual and Non-Regular Structures;151
7.3.5;3.5 Transfer to Mesoscopic Levels;151
7.4;REFERENCES;152
8;Chapter 6 ENHANCED SAMPLING METHODS FOR ATOMISTIC SIMULATION OF NUCLEIC ACIDS;155
8.1;1. INTRODUCTION;155
8.2;2. METHODS FOR IMPROVING SAMPLING EFFICIENCY;158
8.2.1;2.1 Continuum Solvation with Low Viscosity;158
8.2.2;2.2 Locally Enhanced Sampling;160
8.2.3;2.3 Replica Exchange Molecular Dynamics;165
8.3;3. SUMMARY;172
8.4;ACKNOWLEDGEMENT;173
8.5;REFERENCES;173
9;Chapter 7 MODELING DNA DEFORMATION;176
9.1;1. DNA DEFORMATION AND ITS BIOLOGICAL INTEREST;176
9.2;2. MODELING STRATEGIES;179
9.2.1;2.1 Building Models of DNA;179
9.2.2;2.2 Controlling Deformations;183
9.2.3;2.3 Enthalpy and Free Energy;185
9.3;3. PRACTICAL APPLICATIONS - FROM THE MACROSCOPIC TO THE MICROSCOPIC;189
9.3.1;3.1 Large Scale Helical Deformations;189
9.3.2;3.2 Deformations of the Base Pairs;194
9.3.3;3.3 Deformations of the Phosphodiester Backbone;201
9.3.4;3.4 Deformation and Recognition;204
9.3.5;3.5 Sequence Induced Fluctuations;208
9.4;REFERENCES;209
10;Chapter 8 MOLECULAR DYNAMICS SIMULATIONS AND FREE ENERGY CALCULATIONS ON PROTEIN-NUCLEIC ACID COMPLEXES;218
10.1;1. INTRODUCTION;218
10.1.1;1.1 Protein-Nucleic Acid Complexes;219
10.1.2;1.2 Molecular Dynamics;220
10.1.3;1.3 Molecular Dynamics of Protein-Nucleic Acid Complexes;221
10.2;2. CASE STUDIES;225
10.2.1;2.1 Catabolite Activator Protein (CAP)-DNA Complex;225
10.2.2;2.2 U1A RNA Complex;229
10.3;3. FREE ENERGY CALCULATIONS;232
10.4;4. SUMMARY;234
10.5;ACKNOWLEDGEMENTS;234
10.6;REFERENCES;234
11;Chapter 9 DNA SIMULATION BENCHMARKS AS REVEALED BY X-RAY STRUCTURES;242
11.1;1. INTRODUCTION;243
11.2;2. METHODS;244
11.2.1;2.1 Database;244
11.2.2;2.2 Conformational Analysis;245
11.2.3;2.3 Deformability;245
11.2.4;2.4 Hydration Patterns;246
11.2.5;2.5 Protein-DNA Contacts;246
11.3;3. RESULTS;247
11.3.1;3.1 Torsion Angles;247
11.3.2;3.2 Base-pair Parameters;249
11.3.3;3.3 Dimeric Structural Variability;254
11.3.4;3.4 Effects of Sequence Context on Dimeric Properties;255
11.3.5;3.5 DNA Hydration;257
11.3.6;3.6 Protein Recognition;259
11.4;4. CONCLUDING REMARKS;261
11.5;ACKNOWLEDGMENTS;262
11.6;REFERENCES;262
12;Chapter 10 RNA: THE COUSIN LEFT BEHIND BECOMES A STAR;265
12.1;1. INTRODUCTION;265
12.2;2. RNA AT ATOMIC RESOLUTION;266
12.3;3. RNA’s DIVERSITY;268
12.4;4. RECENT DISCOVERIES CONCERNING RNA’s STARRING ROLE;269
12.5;5. MAJOR CHALLENGES IN RNA RESEARCH;273
12.5.1;5.1 RNA Gene Location;273
12.5.2;5.2 RNA Gene Function;274
12.5.3;5.3 RNA’s Structural Repertoire;274
12.5.4;5.4 The RNA Folding Problem;275
12.5.5;5.5 Designing Novel RNAs;281
12.6;6. INVITATION TO COMPUTATIONAL BIOLOGISTS;281
12.7;ACKNOWLEDGEMENTS;283
12.8;REFERENCES;283
13;Chapter 11 MOLECULAR DYNAMICS SIMULATIONS OF RNA SYSTEMS: IMPORTANCE OF THE INITIAL CONDITIONS;288
13.1;1. INTRODUCTION;288
13.2;2. VARIOUS ISSUES RELATED TO MD SETUPS;291
13.2.1;2.1 Choosing an Appropriate Starting Structure …;291
13.2.2;2.2 … and Checking it;292
13.3;3. CONCLUSIONS;297
13.4;ACKNOWLEDGEMENTS;298
13.5;REFERENCES;298
14;Chapter 12 MOLECULAR DYNAMICS SIMULATIONS OF NUCLEIC ACIDS;306
14.1;1. GUANINE QUADRUPLEX MOLECULES;307
14.1.1;1.1 Quadruplex Structure;307
14.1.2;1.2 Behavior of the Quadruplex Stem;309
14.1.3;1.3 Behavior of the Quadruplex Loops;313
14.1.4;1.4 Quadruplex Stem Formation;315
14.2;2. MD SIMULATIONS OF RNA MOLECULES;318
14.3;ACKNOWLEDGEMENTS;326
14.4;REFERENCES;326
15;Chapter 13 USING COMPUTER SIMULATIONS TO STUDY DECODING BY THE RIBOSOME;331
15.1;REFERENCES;344
16;Chapter 14 BASE STACKING AND BASE PAIRING;347
16.1;1. INTRODUCTION, METHODS AND PRINICPLES;347
16.1.1;1.1 The Advantage of Ab Initio Studies;347
16.1.2;1.2 The Electron Correlation;351
16.1.3;1.3 Fast Variants of MP2;353
16.1.4;1.4 Basis Set of Atomic Orbitals;354
16.1.5;1.5 Energetics of Molecular Interactions – The Main Task;358
16.1.6;1.6 What QM Calculations Tell About DNA and RNA?;358
16.1.7;1.7 Interplay Between Intrinsic and Environmental Effects;359
16.1.8;1.8 Definition of Interaction Energy and its Components;365
16.1.9;1.9 What is Basis Set Superposition Error (BSSE)?;366
16.1.10;1.10 What are Deformation Energies of Monomers?;367
16.1.11;1.11 Nonplanarity of Amino Groups;369
16.1.12;1.12 Can Strength of Individual H-Bonds be Dissected?;370
16.1.13;1.13 What are the Many Body Effects?;371
16.1.14;1.14 Gradient Optimization vs. Single Points;371
16.1.15;1.15 Atomic Charges;373
16.1.16;1.16 Advance of High-Level Ab Initio Calculations;374
16.2;2. SELECTED RECENT RESULTS;375
16.2.1;2.1 H-bonded Base Pairs;375
16.2.2;2.2 RNA Base Pairing;379
16.2.3;2.3 Nature of Base Stacking;380
16.2.4;2.4 Future Directions: Combined Quantum Mechanical and Molecular Mechanical Approaches;381
16.3;REFERENCES;383
17;Chapter 15 INTERACTION OF METAL CATIONS WITH NUCLEIC ACIDS AND THEIR BUILDING UNITS;393
17.1;1. INTRODUCTION;393
17.2;2. METAL-NUCLEOBASE INTERACTIONS;394
17.3;3. METAL-PHOSPHATE INTERACTIONS;396
17.4;4. METAL-NUCLEOTIDE INTERACTIONS;398
17.5;5. INTERACTION OF METAL CATIONS WITH BASE PAIRS;399
17.6;6. NUCLEIC ACIDS AND METALLODRUGS;401
17.6.1;6.1 Platinated Nucleobases;402
17.6.2;6.2 Interaction Strength of Platinated Base Pairs;404
17.6.3;6.3 Studies on Cisplatin Binding to Nucleobases;405
17.7;7. CATION-INTERACTIONS;407
17.8;8. SITE-SPECIFIC BINDING OF CATIONS TO NUCLEIC ACIDS;408
17.9;9. COMMENT ON THE ACCURACY OF FORCE FIELD CALCULATIONS FOR CATIONS;409
17.10;10. CONCLUSIONS;410
17.11;ACKNOWLEDGEMENTS;411
17.12;REFERENCES;411
18;Chapter 16 PROTON TRANSFER IN DNA BASE PAIRS;415
18.1;1. INTRODUCTION;415
18.2;2. NEUTRAL BASE PAIRS;416
18.3;3. EXCITED BASE PAIRS;419
18.4;4. IONIZED BASE PAIRS;423
18.5;5. PROTONATED BASE PAIRS;425
18.6;6. METAL CATION BINDING;427
18.7;7. CONCLUSIONS;430
18.8;REFERENCES;431
19;Chapter 17 COMPARATIVE STUDY OF QUANTUM MECHANICAL METHODS RELATED TO NUCLEIC ACID BASES: ELECTRONIC SPECTRA, EXCITED STATE STRUCTURES AND INTERACTIONS;437
19.1;1. INTRODUCTION;438
19.2;2. GROUND STATE PROPERTIES OF NUCLEIC ACID BASES AND BASE PAIRS;440
19.3;3. EXCITED STATE PROPERTIES OF NUCLEIC ACID BASES;441
19.3.1;3.1 Electronic Transitions;442
19.3.2;3.2 Geometries;451
19.4;4. EXCITED STATE PROPERTIES OF WATSON-CRICK BASE PAIRS;456
19.5;5. CONCLUDING REMARKS;458
19.6;ACKNOWLEDGEMENTS;458
19.7;REFERENCES;459
20;Chapter 18 SUBSTITUENT EFFECTS ON HYDROGEN BONDS IN DNA;466
20.1;1. INTRODUCTION;466
20.2;2. HYDROGEN BONDS IN NATURAL WATSON-CRICK BASE PAIRS;468
20.2.1;2.1 Structure and Strength of Watson-Crick Hydrogen Bonds;468
20.2.2;2.2 Nature of Watson-Crick Hydrogen Bonds;469
20.2.3;2.3 Orbital Interactions versus Electrostatic Attraction;472
20.3;3. SUBSTITUTIONS IN X–H•••Y HYDROGEN BONDS;474
20.4;4. REMOTE SUBSTITUTIONS AT DNA BASES;477
20.5;5. SUPRAMOLECULAR SUBSTITUENT EFFECTS;482
20.6;6. CONCLUSIONS;485
20.7;ACKNOWLEDGEMENT;486
20.8;REFERENCES;486
21;Chapter 19 COMPUTATIONAL MODELING OF CHARGE TRANSFER IN DNA;488
21.1;1. INTRODUCTION;489
21.2;2. BASICS OF ET THEORY;493
21.3;3. MODELS AND COMPUTATIONAL METHODS;496
21.3.1;3.1 DNA Models;496
21.3.2;3.2 Methods;497
21.4;4. CALCULATION OF CHARGE TRANSFER PARAMETERS;498
21.4.1;4.1 The Driving Force;498
21.4.2;4.2 Effect of DNA Environment on the Free Energy of Charge Transfer;499
21.4.3;4.3 Electronic Coupling;500
21.4.4;4.4 Reorganization Energy;502
21.4.5;4.5 Quantum Chemical Study of CT Rate in DNA;503
21.5;5. EXCESS CHARGE DELOCALIZATION;505
21.6;6. CHARGE TRANSFER MECHANISMS;507
21.7;7. CONCLUDING REMARKS;509
21.8;ACKNOWLEDGEMENTS;510
21.9;REFERENCES;511
22;Chapter 20 QUANTUM CHEMICAL CALCULATIONS OF NMR PARAMETERS;515
22.1;1. INTRODUCTION;515
22.2;2. PARAMETERS OF THE NMR SPECTRUM;516
22.2.1;2.1 Signal Position – Chemical Shift;516
22.2.2;2.2 The Hyperfine-Structure of the NMR Signal;517
22.2.3;2.3 Signal Line-Width and Intensity – Relaxation of Nuclear Spin;520
22.3;3. CALCULATION OF NMR PARAMETERS;525
22.3.1;3.1 Chemical Shift ;527
22.3.2;3.2 The Indirect Spin-Spin Coupling Constant ;528
22.3.3;3.3 Comments on Calculations of NMR Properties;531
22.3.4;3.4 Practical Examples;532
22.4;ACKNOWLEDGEMENT;536
22.5;REFERENCES;536
23;Chapter 21 THE IMPORTANCE OF ENTROPIC FACTORS IN DNA BEHAVIOUR: INSIGHTS FROM SIMULATIONS;539
23.1;1. INTRODUCTION;539
23.2;2. DNA DYNAMICS AND INFORMATION TRANSFER;545
23.2.1;2.1 A Cooperative Ligand-DNA Interaction;545
23.2.2;2.2 Experimental Studies of the Ligand-DNA Complex;546
23.2.3;2.3 Computer Simulations of the Ligand-DNA Complex;547
23.2.4;2.4 Mechanism of Information Transfer;548
23.3;3. ENTROPY AND THE BIOMECHANICS OF DNA;550
23.3.1;3.1 The Biological Importance of DNA Mechanics;550
23.3.2;3.2 The Disagreement between Nanomanipulation Experiments and MD Simulation;550
23.3.3;3.3 Quasi-static Simulations of DNA Stretching;554
23.3.4;3.4 The Entropic Instability of S-ladder DNA;556
23.3.5;3.5 Implications for the Action of Molecular Motors;558
23.4;4. CONCLUSIONS;558
23.5;REFERENCES;559
24;Chapter 22 SEQUENCE-DEPENDENT HARMONIC DEFORMABILITY OF NUCLEIC ACIDS INFERRED FROM ATOMISTIC MOLECULAR DYNAMICS;561
24.1;1. HIGH-DIMENSIONAL AND REDUCED MODELS;561
24.2;2. INFERRING DNA SHAPE AND DEFORMABILITY FROM STRUCTURAL FLUCTUATIONS;566
24.3;3. APPLICATIONS;571
24.4;4. COMPARISON TO EXPERIMENTALLY BASED FORCE FIELDS;573
24.5;5. CONCLUSIONS AND PERSPECTIVES;576
24.6;ACKNOWLEDGEMENTS;577
24.7;REFERENCES;577
25;CHROMATIN SIMULATIONS;606
25.1;1. INTRODUCTION;606
25.2;2. COARSE-GRAINED MODELS OF DNA;609
25.2.1;2.1 DNA flexible Wormlike Chain – Nanomechanical Parameters;609
25.3;3. SIMULATION PROCEDURES;612
25.3.1;3.1 Monte-Carlo Simulations;612
25.3.2;3.2 Brownian Dynamics Simulations;613
25.4;4. NUCLEOSOMES;614
25.4.1;4.1 Nucleosome Structure;614
25.4.2;4.2 Nucleosome Unwrapping – Analytical Model;615
25.4.3;4.3 Brownian Dynamics Simulation of Nucleosome Unwrapping;618
25.4.4;4.4 A Possible Mechanism for Nucleosome Unwrapping;619
25.5;5. COARSE-GRAINED MODELS OF CHROMATIN;621
25.5.1;5.1 Persistence Length of Chromatin;622
25.5.2;5.2 Tail Bridging for Nucleosome Attraction;623
25.5.3;5.3 Simulation of Chromatin Fiber Stretching;625
25.6;REFERENCES;629
26;INDEX;636
Chapter 7 MODELING DNA DEFORMATION (p. 169-170)
Péter Várnai1,2 and Richard Lavery11Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, Paris 75005, France
2University of Cambridge,Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, United Kingdom
Abstract: Deformations of DNA contribute to its essential biological function. In our laboratory, we have been studying both local and global deformations of DNA and their relationship to base sequence by molecular modeling and simulation techniques. In the current chapter, we first give an overview of the various approaches used in our laboratory to build DNA models and to control DNA deformations. Notably, we discuss the JUMNA program that uses internal and helicoidal variables, and also umbrella sampling free energy simulations used to follow DNA deformations. In the second part, we summarize the results these techniques enabled us to obtain, starting from the large scale deformations, such as stretching, twisting and bending, down to the more local changes involving base opening and flipping and backbone conformations. A separate section deals with the sequence specific recognition of DNA by proteins and the role of DNA deformation in the process. We hope to show the reader that theoretical studies can play a significant role in obtaining a better understanding of this fascinating biopolymer.
Key words: DNA deformation, recognition, base flipping, single molecule manipulation, internal coordinates, JUMNA, AMBER, umbrella sampling, free energy, MMPBSA
1. DNA DEFORMATION AND ITS BIOLOGICAL INTEREST
At first sight, DNA seems to be a relatively simple biopolymer. While it is a heteropolymer, it is composed of only four different nucleotides, a small number compared to the 20 amino acids which constitute the polypeptide chain of proteins. This simplicity led early researchers to initially reject DNA as the potential carrier of genetic information. While the beautiful double helical structure proposed by Watson and Crick1,2 and the subsequent discovery of the triplet genetic code,3,4 explained how DNA could stock enormous amounts of information, it again suggested that structurally there was not much to study. At the core of the double helical structure was the observation that the spiral phosphodiester backbones could accommodate any Watson-Crick base pair sequence without deformation.
The first step to refining this viewpoint comes from realizing that DNA must be packed quite densely to fit into a cell. This is easily illustrated in the case of human cells which contain around 1 m of DNA (corresponding to 4 x 109 base pairs) in a nucleus within a diameter of only a few microns. Within sperm heads, the packing density is even higher. A partial explanation of how this is achieved comes from modeling DNA as a flexible rod, which naturally forms a random coil to increase its conformational entropy. But this factor alone only is not enough to account for the packing that occurs within the nucleus. As we now know, the remainder is due to protein-induced superhelical compaction leading to the complex and hierarchical structure of chromatin.
A second type of deformation was detected early in the study of DNA and concerns its overall helical form. Fiber diffraction studies already showed that the double helical structure could be modified as a function of its solvent and counterion environment. The A and B forms of the double helix first named by Rosalind Franklin5 are now structurally well-characterized and they have been joined by many other conformational families which go even further in tampering with DNA structure, by modifying its helical chirality, changing its number of strands, its base pairing and its relative strand orientations. In recent years, structural studies have been joined by single molecule manipulation experiments which offer us a new way to directly probe the mechanical properties of DNA.6 These experiments have again showed that DNA is more complex than initially expected and that, when pulled or twisted, it can undergo transitions to new and unexpected conformations.
