생명 정보학

1. Molecular Biology and Biological Chemistry 1

The Genetic Material 2
Nucleotides 2
Orientation 3
Base pairing 5
The central dogma of molecular biology 7

Gene Structure and Information Content 8
Promoter sequences 8
The genetic code 9
Open reading frames 10
Introns and exons 13

Protein Structure and Function 14
Primary structure 14
Secondary, tertiary, and quaternary structure 16

The Nature of Chemical Bonds 16
Anatomy of an atom 17
Valence 19
Electronegativity 20
Hydrophilicity and hydrophobicity 21
Chapter Summary 22
Readings for Greater Depth 22
Questions and Problems 23

2. Data Searches and Pairwise Alignments 25
Dot Plots 26
Simple Alignments 28
Gaps 29
Simple gap penalties 29
Origination and length penalties 30

Scoring Matrices 31
Dynamic Programming: The Needleman and Wunsch
Algorithm 35
Global and Local Alignments 39
Semiglobal alignments 39
The smith-waterman algorithm 41

Database Searches 43
BLAST and Its relatives 43
FASTA and related algorithm n 45
Alignment scores and statistical significance of database searches 47

Multiple Sequence Alignments 48
Chapter Summary 49
Readings for Greater Depth 50
Questions and Problems 51

3. Substitution Patterns 53
Patterns of Substitutions within Genes 54
Mutation rates 54
Functional constraint 55
Synonymous vs. nonsynonymous substitutions 57
Indels and pseudogenes 58
Substitutions vs. mutations 59
Fixation 60

Estimating Substitution Numbers 62
Jukes-cantor model 63
Transitions and transversions 64
Kimura's two-parameter model 64
Models with even more parameters 66
Substitutions between protein sequences 67

Variations in Evolutionary Rates between Genes 68
Molecular Clocks 69
Relative rate test 70
Causes of rate variation in lineages 72

Evolution in Organelles 72
Chapter Summary 73
Readings for Greater Depth 74
Questions and Problems 74
4. Distance-Based Methods of Phylogenetics 77
History of Molecular Phylogenetics 78
Advantages to Molecular Phylogenies 79
Phylogenetic Trees 81
Terminology of tree reconstruction 81
Rooted and unrooted trees 82
Gene vs. species trees 84
Character and distance data 85

Distance Matrix Methods 87
UPGMA 87
Estimation of branch lengths 90
Transformed distance method 91
Neighbor's relation method 93
Neighbor-joining methods 94

Maximum Likelihood Approaches 95
Multiple Sequence Alignments 95
Chapter Summary 96
Readings for Greater Depth 97
Questions and Problems 97

5. Character-Based Methods of Phylogenetics 99
Parsimony 100
Informative and uninformative sites 100
Unweighted parsimony 102
Weighted parsimony 106

Inferred Ancestral Sequences 107
Strategies for Faster Searches 108
Branch and bound 108
Heuristic searches 110
Consensus Trees 112
Tree Confidence 112
Bootstrapping 113
Parametric tests 115

Comparison of Phylogenetic Methods 116
Molecular Phylogenies 116
The tree of life 116
Human origins 118

Chapter Summary 119
Readings for Greater Depth 119
Questions and Problems 120

6. Genomics and Gene Recognition 121
Prokaryotic Genomes 122
Prokaryotic Gene Structure 124
Promoter elements 125
Open Reading frames 128
Conceptual translation 129
Termination sequences 129

GC Contents in Prokaryotic Genome 130
Prokaryotic Gene Density 131
Eukaryotic Genomes 131
Eukaryotic Gene Structure 132
Promoter elements 133
Regulatory protein binding sites 136
Open Reading Frames 137
Introns and exons 138
Alternative splicing 139

GC Content in Eukaryotic Genomes 141
CpG islands 143
Isochores 145
Codon usage bias 147

Gene Expression 147
cDNAs and ESTs 147
Serial analysis of gene expression 149
Microarrays 150

Transposition 152
Repetitive Elements 153
Eukaryotic Gene Density 155
Chapter Summary 155
Readings for Greater Depth 156
Questions and Problems 157

7. Protein and RNA Structure Prediction 159
Amino Acids 160
Polypeptide Composition 164
Secondary Structure 164
Backbone flexibility, φ and ψ 164
Accuracy of predictions 166
The chou-fasman and GOR methods 167
Tertiary and Quaternary Structure 169
Hydrophobicity 171
Disulfide bonds 171
Active structures vs. most stable structures 172

Algorithms for Modeling Protein Folding 173
Lattice models 173
Off-lattice models 176
Energy functions and optimization 176

Structure Prediction 178
Comparative modeling 179
Threading: reverse protein folding 180

Predicting RNA Secondary Structures 181
Chapter Summary 183
Readings for Greater Depth 184
Questions and Problems 185

8. Proteomics 187
From Genomes to Proteomes 188
Protein Classification 188
Enzyme nomenclature 189
Families and superfamilies 190
Folds 191

Experimental Techniques 192
2D electrophoresis 192
Mass spectrometry 194
Protein microarrays 195
Inhibitors and Drug Design 196
Ligand Screening 197
Ligand docking 197
Database screening 199

X-Ray Crystal Structures 200
NMR Structures 205
Empirical Methods and Prediction Techniques 206
Post-Translational Modification Prediction 207
Protein sorting 208
Proteolytic cleavage 210
Glycosylation 211
Phosphorylation 211

Chapter Summary 212
Readings for Greater Depth 213
Questions and Problems 214

Glossary 215
Solutions to Odd-Numbered Questions and Problems 217
Index 239