Bioinformation Discovery (eBook)

Preface 6
Acknowledgments 7
Contents 8
List of Figures 13
List of Tables 17
Abbreviations 18
Chapter 1 21
Introduction 21
1.1 Bioinformatics 21
1.2 Bioinformatics-Related Terms 22
1.3 Journals Supporting Bioinformatics 22
1.4 Bioinformatics in Drug Discovery 24
1.5 Skills for Bioinformatics 24
1.6 Bioinformatics Warehousing in Drug Discovery 25
1.7 Bioinformatics Components 25
1.8 Bioinformation 26
1.9 Bioinformatics Variables 27
1.10 Cell Constituents 27
1.10.1 Nucleic Acids 28
1.10.2 Proteins 29
.1.10.3 Classification of Amino Acids 29
1.11 Codon and Codon Usage Table 29
1.12 Bioinformation Discovery 31
1.13 Bioinformatics Principle 31
1.14 Bioinformatics Challenges 32
.1.15 Biological Data 32
.1.16 Data Explosion 34
.1.17 Sequence Data 34
.1.18 Structure Data 34
.1.19 Small Molecules 34
.1.20 Macromolecules 36
1.21 SCOP Dataset 37
1.22 CATH Dataset 38
.1.23 Function Data 40
.1.24 Pathways Data 40
.1.25 Bioinformatics Developments 41
.1.26 Discovery Environment 41
.1.27 Sequence, Structure Alignment and Evolutionary Inferences 42
1.28 Molecular Modeling 44
1.28.1 Protein Modeling 44
1.28.2 Methods of Protein Modeling 45
1.28.3 Caveats on Homology Modeling 46
1.29 Exercises 46
Chapter 2 47
Creating Datasets 47
2.1 .Datasets 47
2.2 .HLA-Binding Peptide Dataset 49
2.3 .MHC–Peptide Structural Dataset 49
2.4 .MHC–Peptide Structure Dataset Clustering 52
2.5 .PDB Chain Identifier 52
2.6 .Information Redundancy in Dataset 56
2.7 .Information from MHC-Peptide Data 56
2.8 .Structural Parameters for MHC–Peptide Dataset Analysis 57
2.9 .Creation of Heterodimer and Homodimer Dataset 57
2.10 .Homodimer Folding Dataset 57
2.11 .Alanine-Mutated Interface Residues Dataset 57
2.12 .Intronless Genes Dataset 79
2.13 .Human Single Exon Gene (SEG) Dataset 81
2.14 .Intron-Containing Genes Dataset 81
2.15 .Fusion Protein Dataset 82
2.16 .Exercises 83
References 84
Chapter 3 85
Tools and Techniques 85
3.1 Align 85
3.2 BIMAS 86
3.3 BLAST 86
3.4 ClustalW 88
3.5 DeCypher 89
3.6 DeepView 89
3.7 FASTA 89
3.8 Insight II 89
3.9 Genscan 90
3.10 GROMOS 90
3.11 HBPLUS 90
3.12 Lalign/Plalign 91
3.13 Ligplot 91
3.14 LOOK 91
3.15 Modeller 92
3.16 NACCESS 93
3.17 Phylip 93
3.18 ProtParam 94
3.19 Protorp 94
3.20 Psap 94
3.21 Ppsearch 94
3.22 Pymol 94
3.23 Rasmol 94
3.24 Rosetta Design 95
3.25 Surfnet 95
3.26 Sybyl 95
3.27 T-Epitope Designer 95
3.28 Exercises 95
References 96
Chapter 4 98
Protein Subunits Interaction 98
4.1 Protein Subunit Interaction 98
Dimer Datasets in Literature 99
4.3 Parameters in Subunit Interaction 100
4.3.1 Hydrophobic Effect 100
4.3.2 Interface Size 101
4.3.3 Interface H-Bonds 101
4.3.4 Interface Residues 103
4.3.5 Interface Residue Type 103
4.3.6 Inferences on Protein Subunit Interactions 104
4.4 Exercises 104
References 105
Chapter 5 106
Homodimer Folding and Binding 106
5.1 Importance of Homodimers 106
Homodimer Folding 107
5.3 Homodimer Structures in Folding 108
5.4 Size, Interface Area and Structure 108
5.5 Interface to Total Residues 111
5.6 Exterior, Interior and Interface Hydrophobicity in 2S and 3S 112
5.7 Folding and Binding Mechanism 113
5.8 Concluding Remarks 115
5.9 Exercises 115
References 115
Chapter 6 116
Fusion Proteins 116
6.1 Gene Fusion 116
6.2 Operons in Prokaryotes as Human Fusion Proteins 117
6.3 Multiple Functions in Fusion Proteins 119
6.4 Alternative Splicing in Fusion Genes 120
6.5 Protein Subunit Interaction and Fusion Proteins 120
6.6 Mechanism of Gene Fusion 121
6.7 Hypothesis of Gene Fusion 121
6.8 Structural Importance of Fusion Proteins 121
6.8.1 Fusion Protein IGPS Function 122
6.8.2 Fusion Protein IGPS Structure 123
6.8.3 IGPS Sequence, Structure and Properties 124
6.8.4 Interface Area in IGPS 125
6.8.5 Gap Volume in IGPS 125
6.8.6 Radius of Gyration in IGPS 127
6.8.7 Structural Features of Fusion Protein IGPS 127
6.9 Exercises 128
References 129
Chapter 7 130
Major Histocompatibility Complex (MHC) and Peptide Binding 130
7.1 MHC Biology and Diversity 130
7.2 Promise of MHC in Medicine 133
7.3 MHC Structure and Function 133
7.3.1 Class I MHC Structure and Function 134
Class II MHC Structure and Function 137
7.4 MHC-Peptide Motifs 139
7.4.1 Class I MHC-Peptide Motifs 139
7.4.2 Class II MHC-Peptide Motifs 140
MHC-Peptide Binding 141
7.6 MHC Polymorphism and Specificity 142
7.7 MHC-Peptide Complex in T-Cell-Mediated Immune Response 142
7.8 MHC-Peptide Binding Predictions 143
7.8.1 Data-Driven Methods 143
7.8.1.1 Limitations in Data-Driven Methods 144
7.8.2 Molecular Modeling Methods 145
7.8.2.1 Class I MHC-Peptide Binding Prediction 145
Class II MHC-Peptide Binding Prediction 146
7.8.3 Limitations in Molecular Modeling Methods 146
7.9 Application 146
7.10 Exercises 147
References 147
Chapter 8 150
HLA Supertypes 150
8.1 HLA Supertypes: Definition 150
.8.2 Grouping of HLA Alleles by Several Research Groups 152
8.3 Perplexing Issues with HLA Supertypes 153
8.4 Structural Basis for HLA Supertypes 153
8.5 Predictive Grouping of HLA Supertypes 155
8.6 Grouping Using Electrostatic Distribution Maps 156
8.7 Concluding Remarks 156
8.8 Exercises 157
References 157
Chapter 9 159
T-Epitope Designer 159
9.1 HLA-Peptide Binding and Its Prediction 159
9.2 Available Prediction Servers 160
9.3 T-Epitope Designer 160
9.4 Model 160
User Interface 162
9.6 Input Data 162
9.7 Output Result 163
9.8 Conclusion 163
9.9 Cautionary Note 163
9.10 Exercises 164
References 164
Chapter 10 166
Eukaryotic Genes, Functions, Genomes, Design, and Evolution 166
10.1 Eukaryotic Genes and Genomes 166
10.2 SEGE 168
10.3 Genome SEGE 168
10.4 Human Single Exon Genes 169
10.5 U-Genome 171
10.6 ExInt 171
Alternative Splicing 172
10.8 Intron and Exon Content in Genomes 173
10.9 Exon–Intron Length Patterns 174
10.10 Intron Organization and Evolution 175
10.11 Exercises 176
References 177
Index 180