Chemical Biology 2006
Book Details:
* Number Of Pages: 265 PDF (5.39 mb)
* Publication Date: 2006-08-30
* ISBN / ASIN: 0470090642
* Manufacturer: Wiley
Book Description:
This book provides an up-to-date guide to chemical biology. It is a modular textbook that brings together the tools and techniques used by physical scientists and makes them available to biological and biomedical scientists. Tools and techniques are explained at a suitable level and the book addresses topical chemical biology questions within each chapter.
Contents:
1 Introduction 1
1.1 Chemical biology – the present 1
1.2 Chemical biology – the past 2
1.3 Chemical biology – the future 3
1.4 Chemical biology – mind the interdisciplinary gap 4
1.5 An introduction to the following chapters 5
1.5.1 Cryo-electron microscopy 5
1.5.2 Atomic force microscopy 5
1.5.3 Differential scanning calorimetry in the study of lipid structures 6
1.5.4 Membrane potentials and membrane probes 6
1.5.5 Identification and quantification of lipids using
mass spectroscopy 7
1.5.6 Liquid-state NMR 7
1.5.7 Solid-state NMR in biomembranes 7
1.5.8 Molecular dynamics 8
1.5.9 Two-dimensional infrared studies of biomolecules 8
1.5.10 Biological applications of single and two-photon fluorescence 8
1.5.11 Optical tweezers 9
1.5.12 PET imaging in chemical biology 9
1.5.13 Chemical genetics 9
2 Cryomicroscopy 11
2.1 The need for (electron) microscopy 11
2.2 Development of cryomicroscopy 11
2.3 Sample–electron interaction 13
2.4 Contrast in negatively stained and cryo preparations 14
2.5 Image formation 16
2.6 Image analysis 16
2.7 Software used in the analysis of electron micrographs 19
2.8 Examples 21
2.8.1 Two-dimensional crystals 21
2.8.2 Helical structures 21
2.8.3 Single particles with low symmetry 24
2.8.4 Cellular tomography 24
2.9 Conclusions 27
3 Atomic force microscopy: applications in biology 29
3.1 A brief history of microscopy 29
3.2 The scanning probe microscope revolution 30
3.2.1 The stylus profiler 30
3.2.2 The scanning tunnelling microscope 30
3.2.3 The atomic force microscope 31
3.3 The workings of an AFM instrument 31
3.3.1 The imaging probe 31
3.3.2 The piezoelectric scanner 32
3.3.3 The deflection detection system 33
3.3.4 The electronic feedback system 34
3.4 Imaging biological molecules with force 34
3.4.1 Contact mode 35
3.4.2 Oscillating cantilever imaging modes 36
3.4.3 Imaging in liquid 38
3.5 Factors influencing image quality 38
3.5.1 Sample preparation and immobilization 38
3.5.2 Tip convolution/broadening 39
3.5.3 Double tipping 40
3.5.4 Sample roughness 41
3.5.5 Temperature variation and vibration isolation 41
3.6 Biological applications of AFM and recent developments 42
3.6.1 Imaging dynamic processes 42
3.6.2 Measuring biomolecular forces 43
3.7 Conclusions and future directions 45
4 Differential scanning calorimetry in the study
of lipid structures 47
4.1 Introduction 47
4.2 Membranes, lipids and lipid phases 47
4.3 Heat exchanges and calorimetry 50
4.3.1 Heat and related entities 50
4.3.2 Differential scanning calorimetry 52
4.4 Phase transitions in pure lipid–water systems 53
4.4.1 Tilted Gel ?Lb0 ? to rippled ?Pb0 ? phase transition (the ‘pre-transition’) 53
4.4.2 Rippled ?Pb0 ? to liquid-crystalline ?La? phase transition 54
4.4.3 Gel ?Lb? to liquid-crystalline ?La? phase transition 55
4.4.4 Lamellar ?La? to inverted hexagonal ?HII? phase transition 55
4.5 Selected examples of transitions in lipid mixtures 55
4.5.1 Phospholipid–cholesterol mixtures 57
4.5.2 Lamellar-to-inverted hexagonal transitions 60
4.6 Complex systems: lipid–protein mixtures and cell membranes 62
4.6.1 Lipid–protein systems 62
4.6.2 Cell membranes and cell walls 64
4.7 Conclusion 65
5 Membrane potentials and membrane probes 67
5.1 Introduction: biological membranes; structure and electrical properties 67
5.2 Phospholipid membranes as molecular environments 68
5.3 The physical origins of the transmembrane ?Vm or ?
surface ?S? and dipolar ?D? membrane potentials 69
5.3.1 The transmembrane potential difference ?Vm or ? 69
5.3.2 The membrane surface potential ?s? 71
5.3.3 The membrane dipole potential ?d? 73
5.4 Measurement of membrane potentials 74
5.4.1 Electrodes 74
5.4.2 Spectroscopic measurements of the transmembrane potential difference 77
5.4.3 Spectroscopic measurements of the membrane surface potential 78
5.4.4 Spectroscopic measurements of the membrane dipole potential 79
5.5 Problems with spectroscopic measurements of membrane potentials 82
5.6 Spatial imaging of membrane potentials 82
6 Identification and quantification of lipids using mass
spectrometry 85
6.1 Introduction 85
6.2 Lipid analysis by mass spectrometry 86
6.2.1 HPLC-ESI-MS 88
6.2.2 Tandem mass spectrometry 91
6.3 Conclusion 93
7 Liquid-state NMR 95
7.1 Introduction 95
7.2 How NMR works: the basics 96
7.3 Some NMR applications in biology 100
7.3.1 In vivo cell metabolism made ‘visible’ by NMR 100
7.3.2 In vivo phosphorus and nitrogen metabolism 101
7.3.3 Identification and quantification of small quantities in a
complex mixture by 2D 1H–31 P-HMQC-TOCSY NMR 104
7.3.4 Simultaneous separation and identification of very
complex mixtures: LC-NMR 106
7.3.5 Three-dimensional molecular structures in solution 108
7.4 Conclusion 111
8 Solid-state NMR in biomembranes 113
8.1 Introduction 113
8.2 NMR basics for membrane systems 114
8.2.1 Anisotropy of NMR interactions in membranes 114
8.2.2 Spectra and the effect of motional averages 116
8.2.3 A special case of motional averaging: magic angle sample spinning 118
8.2.4 Relaxations times: measuring dynamics 118
8.3 Applications of wide-line NMR to membrane systems 119
8.3.1 Lipid phases: diagrams, peptide-induced fusion–fragmentation 120
8.3.2 Bilayer internal dynamics: order parameters, membrane
thickness, sterols 121
8.3.3 Orientation of molecules (sterols, helical peptides) in membranes 124
8.3.4 Membrane dynamics from picoseconds to milliseconds 124
8.4 Applications of MAS to biomembranes and natural colloids 126
8.4.1 Three-dimensional structure of peptides in membranes 126
8.4.2 Three-dimensional structure of wine tannin–salivary
protein colloidal complexes 128
8.4.3 Distance determination using MAS recoupling techniques 128
8.5 Conclusion 128
9 Molecular dynamics 133
9.1 Introduction 133
9.2 The basis of molecular mechanics 133
9.2.1 Force fields 134
9.2.2 The energy problem 135
9.3 The basis of molecular dynamics 137
9.3.1 Influence of temperature 138
9.4 Factors affecting the length of simulations 139
9.5 Problems caused by solvents 140
9.6 How to build a lipid bilayer for simulation purposes 142
9.7 Special case of membrane proteins 146
9.8 Summary 149
10 Two-dimensional infrared studies of biomolecules 151
10.1 Introduction 151
10.2 Description of the technique 152
10.3 Spectral simulations 152
10.3.1 Intensity changes 154
10.3.2 Band shifting 156
10.3.3 Bandwidth 157
10.4 Two-dimensional studies of human lipoproteins 158
10.5 Summary 161
11 Biological applications of single- and two-photon fluorescence 163
11.1 Introduction 163
11.2 Basic principles of fluorescence 163
11.3 Main principles of RET via single-photon excitation 164
11.4 Detection of RET 165
11.4.1 Steady-state method 165
11.4.2 Time-resolved method 166
11.5 Biological examples of RET monitored by frequency-domain FLIM 168
11.6 Two-photon fluorescence 171
11.6.1 Basic concepts 171
11.6.2 Two-photon fluorescence 174
11.7 Applications of two-photon fluorescence 178
11.7.1 Two-photon fluorescence imaging 178
11.7.2 Biological example – two-photon time-domain FLIM 184
11.8 Photoselection and fluorescence anisotropy 185
11.9 Fluorescence anisotropy and isotropic rotational diffusion 185
11.10 Fluorescent probes in proteins and membranes 188
11.10.1 Ordered molecular systems 190
11.11 Future developments 193
11.11.1 New chromophores for two-photon fluorescence 193
11.11.2 Stimulated emission depletion in two-photon excited states 193
11.12 Conclusions 196
12 Optical tweezers 199
12.1 Introduction 199
12.1.1 History of optical tweezers 199
12.1.2 Single-molecule studies 200
12.2 Theoretical background 201
12.3 Apparatus 203
12.3.1 Building an optical tweezers transducer 203
12.3.2 Creating multiple laser traps: acousto-optical deflectors 204
12.3.3 Camera and light path 206
12.4 Data collection and analysis 207
12.4.1 Collecting data with an optical tweezer 207
12.4.2 Calibration of the detectors and of the optical tweezer stiffness 208
12.4.3 Stokes calibration 208
12.4.4 Equipartition principle 208
12.5 A biological application 209
12.5.1 Studying acto-myosin interactions 209
12.5.2 Identification of events and data analysis 211
12.5.3 Measuring the powerstroke 211
12.5.4 Lifetime analysis 213
12.6 Other biological examples 214
12.7 Summary 216
13 PET imaging in chemical biology 217
13.1 Introduction 217
13.2 Positron emission tomography: principles and instrumentation 218
13.3 Applications of PET imaging in the biomedical sciences 220
13.3.1 A labelled glucose analogue: an indirect probe
to measure energy metabolism 221
13.3.2 Imaging dopamine metabolism with PET 222
13.3.3 PET imaging in gene expression 224
13.3.4 Molecular imaging in drug discovery and development 226
13.4 Conclusions and outlook 228
14 Chemical genetics 231
14.1 Introduction 231
14.2 Why chemicals? 232
14.3 Chemical genetics – why now? 233
14.4 The relationship between classical genetics and chemical genetics 234
14.5 Forward chemical genetics 235
14.5.1 Obtain a compound library 236
14.5.2 Screening 242
14.5.3 Target identification 244
14.6 Reverse chemical genetics 245
14.7 Closing remarks 247
Index 249
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