Practical Bioinformatics (eBook)

Preface 5
Contents 7
Contributors 14
Computational Methods for Protein Structure Prediction and Fold Recognition 17
1 Primary Structure Analysis 17
2 Secondary Structure Prediction 21
3 Protein Fold-Recognition 24
4 Predicting All-in-One-Go 28
5 Pitfalls of Fold Recognition 30
References 32
‘Meta’Approaches to Protein Structure Prediction 38
1 Introduction 38
2 The Utility of Servers as Standard Tools for Protein Structure Prediction 39
3 Future Prospects 46
References 47
From Molecular Modeling to Drug Design 50
1 Introduction 50
2 Comparative Modeling 53
3 Model-Based Drug Design 67
4 Conclusions 77
References 78
Structure Determination of Macromolecular Complexes by Experiment and Computation 87
1 Introduction 87
2 Hybrid Approaches to Determination of Assembly Structures 91
3 Comparative Modeling for Structure Determination of Macromolecular Complexes 96
4 Conclusions 105
References 106
Modeling Protein Folding Pathways 111
1 Introduction: Darwin Versus Boltzmann 111
2 Knowledge-Based Models for Folding Pathways 113
3 ROSETTA: Folding Simulations Using a Fragment Library 115
4 HMMSTR-CM: Folding Pathways Using Contact Maps 120
5 Conclusions 132
References 132
Structural Bioinformatics and NMR Structure Determination 137
1 Introduction: NMR and Structural Bioinformatics 137
2 Algorithms for NMR Structure Calculation 138
3 Internal Dynamics and NMR Structure Determination 141
4 Structure Validation 142
5 Structural Genomics by NMR 143
6 Databanks and Databases 146
7 Conclusions 147
References 148
Bioinformatics-Guided Identification and Experimental Characterization of Novel RNA Methyltransferases 152
1 Introduction 152
2 Traditional and Novel Approaches to Identification of New RNA- Modification Enzymes 158
3 Bioinformatics: Terminology, Methodology, and Applications to RNA MTases 159
4 Conclusions 173
References 175
Finding Missing tRNA Modification Genes: a Comparative Genomics Goldmine 182
1 Missing tRNA Modification Genes 182
2 Comparative Genomics: an Emerging Tool to Identify Missing Genes 186
3 Finding Genes for Simple tRNA Modifications 188
4 Finding Complex Modification Pathway Genes 191
5 Conclusions 196
References 197
Evolution and Function of Processosome, the Complex that Assembles Ribosomes in Eukaryotes: Clues from Comparative Sequence Analysis 204
1 Introduction 204
2 Sequence Analysis of the Processosome Components 205
3 Phyletic Patterns 225
4 Concluding remarks 229
References 230
Bioinformatics-Guided Experimental Characterization of Mismatch- Repair Enzymes and Their Relatives 233
1 Introduction 233
2 Sau3AI – Similar Folds for N- and C-Terminal Domains 237
3 Identification of the Methylation Sensor of MutH 244
A 248
B 248
C 248
4 Conclusions 250
References 251
Predicting Functional Residues in DNA Glycosylases by Analysis of Structure and Conservation 254
1 Introduction 254
2 Generating Predictions: Sequence Selection and Analysis 255
3 Testing the Predictions: Mutational Analysis of Residues Defining Substrate Specificity in Formamidopyrimidine- DNA Glycosylase 262
4 Refining the Predictions: Analysis of Substrate Specificity in the Endonuclease III Family 265
References 270
Subject Index 273