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Biophysics is a rapidly-evolving interdisciplinary science that applies theories and methods of the physical sciences to questions of biology. Biophysics encompasses many di… Read more
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Immediately download your ebook while waiting for your print delivery. No promo code needed.
Biophysics is a rapidly-evolving interdisciplinary science that applies theories and methods of the physical sciences to questions of biology. Biophysics encompasses many disciplines, including physics, chemistry, mathematics, biology, biochemistry, medicine, pharmacology, physiology, and neuroscience, and it is essential that scientists working in these varied fields are able to understand each other's research. Comprehensive Biophysics, Nine Volume Set will help bridge that communication gap.
Written by a team of researchers at the forefront of their respective fields, under the guidance of Chief Editor Edward Egelman, Comprehensive Biophysics, Nine Volume Set provides definitive introductions to a broad array of topics, uniting different areas of biophysics research - from the physical techniques for studying macromolecular structure to protein folding, muscle and molecular motors, cell biophysics, bioenergetics and more. The result is this comprehensive scientific resource - a valuable tool both for helping researchers come to grips quickly with material from related biophysics fields outside their areas of expertise, and for reinforcing their existing knowledge.
Researchers, advanced undergraduate and graduate students, postdoctoral fellows, senior investigators, corporate customers (such as biotech companies) and libraries from Physics, Chemistry and Life Sciences departments
Editorial Board
Preface
Permission Acknowledgments
Volume 1 Biophysical Techniques for Structural Characterization of Macromolecules
1.1 Volume Introduction
Overview and Historical
1.2 Cantor and Schimmel – 30 Years Later
Protein Production Strategies for High-Throughput Structure Determination
1.3 Efficient Strategies for Production of Eukaryotic Proteins
Glossary
1.3.1 Introduction
1.3.2 Selection of Expression Platform
1.3.3 Cloning
1.3.4 Expression and Recovery of Target Protein
1.3.5 Facility
1.3.6 Rescue and Optimization Strategies
1.3.7 Conclusion
Acknowledgments
REFERENCES
X-ray Crystallography
1.4 X-Ray Crystallography: Crystallization
Glossary
1.4.1 Introduction
1.4.2 Structure Determination Process Overview
1.4.3 Precrystallization Studies
1.4.4 Crystallization Process
1.4.5 High-Throughput Crystallization
REFERENCES
1.5 X-Ray Crystallography: Data Collection Strategies and Resources
Glossary
1.5.1 Basic Concepts in X-Ray Crystal Diffraction
1.5.2 X-Ray Sources and Instrumentation
1.5.3 Data Collection Strategies
REFERENCES
1.6 Phasing of X-ray Data
1.6.1 The Phase Problem or What Can Go Wrong?
1.6.2 Direct Methods: What We Know About the Unmeasured Phases?
1.6.3 The Patterson Function: Who Needs the Phases?
1.6.4 Dual-Space Recycling: Enforcing Atomicity in Real and Reciprocal Space
1.6.5 Experimental Phasing: Divide and Conquer
1.6.6 Density Modification: Improving Experimental Phases
1.6.7 Molecular Replacement: Exploiting Previous Structural Information
1.6.8 Frontier Methods: Not General – Yet?
1.6.9 Multiple Beam Interference: But It Is Possible to Measure Phases
1.6.10 Multisolution Combination of Location of Model Fragments and Density Modification
1.6.11 Molecular Replacement with Homology Models
Appendix: Web Phasing
Acknowledgments
REFERENCES
1.7 Refinement of X-ray Crystal Structures
Glossary
1.7.1 Introduction
1.7.2 Target Functions for Refinement
1.7.3 The Model
1.7.4 Cross-Validation
1.7.5 Optimization Methods
1.7.6 Special Considerations at Low Resolution
1.7.7 Conclusions and Outlook
Acknowledgments
REFERENCES
1.8 Structure Validation and Analysis
Glossary
1.8.1 Introduction
1.8.2 Validation of Crystallographic Models
1.8.3 Structural Biology in a High-Throughput Environment
1.8.4 Concluding Remarks
1.8.5 Software and Tools for Structure Validation and Analysis
Acknowledgment
REFERENCES
NMR Spectroscopy
1.9 Introduction to Solution State NMR Spectroscopy
1.9.1 Introduction
1.9.2 Introduction to the NMR Experiment
1.9.3 Multidimensional NMR Spectroscopy
1.9.4 Features of the NMR Spectrum
1.9.5 Relaxation Processes and Their Mechanisms
1.9.6 Samples
1.9.7 Resonance Assignments
1.9.8 Heteronuclear Multidimensional NMR Spectra
1.9.9 Problems with Large Molecules
1.9.10 Qualitative Structural Information from the NMR Spectrum
1.9.11 Structure Determination by NMR
1.9.12 Examples of Structures Calculated by NMR
REFERENCES
1.10 Solid State NMR Methods
1.10.1 Introduction
1.10.2 High-Resolution ssNMR
1.10.3 Sample Preparation
1.10.4 From High Resolution to 3-D Structure
1.10.5 Dynamics and Time-Resolved Experiments
1.10.6 Applications to Amyloids and Membrane Proteins
1.10.7 Larger Systems and Hybrid Approaches
1.10.8 Conclusion and Future Directions
Acknowledgments
REFERENCES
1.11 The Hybrid Solution/Solid-State NMR Method for Membrane Protein Structure Determination
1.11.1 Overview
1.11.2 Solution NMR Approach for Membrane Proteins in Micelles
1.11.3 Solid-State NMR Approach for Uniaxially Aligned Membrane Proteins
1.11.4 Computational Approach: Hybrid Energy Function and Virtual Membrane
1.11.5 Examples: High-Resolution Structures and Topologies of Phospholamban (Monomer and Pentamer) and Sarcolipin in Lipid Membranes
1.11.6 Sensitivity and Resolution Enhancement in Separated Local Field Experiments
1.11.7 Conclusions and Perspectives
REFERENCES
1.12 Labeling Techniques
Glossary
1.12.1 Introduction
1.12.2 Basic Isotope Labeling Strategies
1.12.3 Stereo-Array Isotope Labeling Principle
1.12.4 Stereo-Array Isotope Labeling Technologies
1.12.5 SAIL NMR Spectroscopy
1.12.6 Conclusion and Outlook
Acknowledgments
REFERENCES
1.13 NMR Spectroscopy: NMR Relaxation Methods
1.13.1 Introduction
1.13.2 Spin Relaxation and Dynamic Effects on NMR Spectra
1.13.3 Experimental Methods for Solution Laboratory Frame Relaxation Measurements
1.13.4 Experimental Methods for Solution Chemical Exchange Measurements
1.13.5 Methods for Nucleic Acids
1.13.6 Applications
1.13.7 Conclusion
Acknowledgments
REFERENCES
Electron Microscopy
1.14 Structure Determination of Macromolecular Complexes by Cryo-Electron Microscopy in vitro and in situ
Glossary
1.14.1 Introduction
1.14.2 3-D Cryo-EM
1.14.3 Automated Data Acquisition
1.14.4 SPA
1.14.5 CET
1.14.6 Electron Crystallography
1.14.7 Interpretation of EM Maps at the Molecular Level
1.14.8 Conclusions
Acknowledgments
REFERENCES
1.15 Analysis of 2-D Crystals of Membrane Proteins by Electron Microscopy
Glossary
1.15.1 Introduction
1.15.2 Membrane Protein 2-D Crystallization
1.15.3 EM Data Collection for 2-D Crystals
1.15.4 Image Processing for 2-D Crystals
1.15.5 Conclusion
REFERENCES
1.16 Cryo-Electron Microscopy and Tomography of Virus Particles
Glossary
1.16.1 Introduction
1.16.2 Single Particle Reconstruction
1.16.3 Tomography
1.16.4 Data Collection
1.16.5 Data Storage
1.16.6 Data Preprocessing
1.16.7 Single Particle Reconstruction
1.16.8 Tomographic Reconstruction
1.16.9 Data Interpretation
1.16.10 Biological Examples
1.16.11 Future Prospects
Acknowledgments
REFERENCES
Mass Spectrometry
1.17 Mass Spectrometry
Glossary
1.17.1 Introduction
1.17.2 Mass Spectrometry Technology
1.17.3 Functional Proteomics
1.17.4 Structural Proteomics
1.17.5 Characterization of Post-Translational Modifications
1.17.6 Chemical Labeling Approaches
1.17.7 Structural Mass Spectrometry
1.17.8 Conclusion and Future Directions
REFERENCES
SAXS
1.18 Small and Wide Angle X-ray Scattering from Biological Macromolecules and their Complexes in Solution
1.18.1 Introduction
1.18.2 Scattering Basics
1.18.3 Effects of Hydration
1.18.4 Three-Dimensional Reconstruction of Low Resolution Density Maps from SAXS Data
1.18.5 Disordered Peptides and Proteins in Solution: Free Energy Landscape for Denaturation
1.18.6 Calculation of SAXS Profiles for Detergent Micelles and Protein–Detergent Complexes
1.18.7 Combination of SAXS and NMR for Structure Determination of Multi-Domain Proteins
1.18.8 Solution Structure of Small Functional RNAs
1.18.9 Use of Nanogold Markers for SAXS Determination of Intramolecular Distance Distributions
Acknowledgments
REFERENCES
Ultrafast Spectroscopic Techniques
1.19 Ultrafast Structural Dynamics of Biological Systems
1.19.1 Introduction
1.19.2 Time and Length Scales
1.19.3 Principles and Methods of Ultrafast Laser Spectroscopy
1.19.4 Principles and Methods of Ultrafast Structural Dynamics
1.19.5 Applications
1.19.6 Outlook
REFERENCES
EPR and Other Electron Spectroscopies
1.20 Electron Magnetic Resonance
Glossary
1.20.1 A Simple Definition of Electron Spin Resonance and Its Spectroscopic Origins
1.20.2 Basic Elements of a Continuous Wave EMR Spectrum
1.20.3 Biophysical Applications of Electron Magnetic Resonance
1.20.4 Magnetochemistry and Electron Resonance
1.20.5 Magnetic Resonance Transitions and Justification of an Independent Spin Hamiltonian
1.20.6 The Lineshape Model and the Physical Interpretation of Relaxation Times
1.20.7 Further Details Concerning Resonance Spectrometers and the Generation of Spectra
1.20.8 Magnetic Effects in Three Dimensions: Anisotropy and Recovery of Information
1.20.9 Electron-Electron Double Resonance and Saturation Transfer
1.20.10 Pulse Methods
1.20.11 Concluding Remarks: Where One Goes from Here
REFERENCES
Computation
1.21 Computation of Structure, Dynamics, and Thermodynamics of Proteins
1.21.1 Introduction
1.21.2 Force Fields
1.21.3 Techniques
1.21.4 Use of Experimental Information in Simulations
1.21.5 Summary and Future Directions
REFERENCES
Fast Flow
1.22 Rapid Mixing Techniques for the Study of Enzyme Catalysis
1.22.1 Background
1.22.2 The Design of Rapid Mixers
1.22.3 Specialized Stopped-Flow and Continuous-Flow Instruments
1.22.4 Rapid Freeze Quenching Techniques
1.22.5 Conclusions and Outlook
Acknowledgments
REFERENCES
Other Spectroscopy – UV-Vis, CD, Raman, Vibrational CD Applied in Biophysical Research
1.23 Optical Spectroscopy
1.23.1 Introduction
1.23.2 Theory
1.23.3 Applications of Absorption and Electronic Circular Dichroism Spectroscopy
1.23.4 IR and Vibrational Circular Dichroism Spectroscopy
1.23.5 Epilogue
REFERENCES
FRET/Fluorescence
1.24 Fluorescence and FRET: Theoretical Concepts 101
1.24.1 Introduction
1.24.2 A Historical Synopsis of the Beginnings of Fluorescence and the Emergence of a Quantitative Physical Model
1.24.3 Fluorescence Background Important for FRET
1.24.4 Pathways of Excited States
1.24.5 FRET History and the Theoretical Basis of FRET
1.24.6 Methods of Data Acquisition and Analysis of FRET (Steady State and Dynamic Time and Frequency Domain)
1.24.7 Postscript
REFERENCES
Volume 2 Biophysical Techniques for Characterization of Cells
2.1 Volume Introduction
Elucidating Cellular Structures
2.2 Confocal Microscopy
2.2.1 Introduction
2.2.2 Flying-Spot Microscopes
2.2.3 Beam Scanning Confocal Microscopes
2.2.4 Scanning and Descanning the Beam
2.2.5 Confocal Imaging at Different Wavelengths
2.2.6 Detector Aperture
2.2.7 Resolution in an Ideal Confocal Microscope
2.2.8 Photon Statistics
2.2.9 Direct View
2.2.10 General Testing of Environmental Effects
2.2.11 Test Slides
Optical Appendix
REFERENCES
2.3 Fluorescence Lifetime Microscopy: The Phasor Approach
2.3.1 Introduction
2.3.2 Methods for the Determination of Fluorescence Lifetime on a Pixel Basis
2.3.3 Methods of Data Analysis
2.3.4 Examples of Application of Phasor Analysis in FLIM
2.3.5 FRET Biosensors
REFERENCES
2.4 Super-Resolution Microscopy
Glossary
2.4.1 Introduction
2.4.2 Super-Resolution Fluorescence Microscopy
2.4.3 Practical Considerations
2.4.4 Conclusions
REFERENCES
2.5 Studying the Macromolecular Machinery of Cells in situ by Cryo-Electron Tomography
Glossary
2.5.1 Introduction
2.5.2 Theoretical Aspects of Three-Dimensional Cryo-Electron Microscopy
2.5.3 From TEM Images to Tomogram
2.5.4 Sample Preparation
2.5.5 Post-Processing and Analysis of Tomograms
2.5.6 CET Studies of Cells and Cellular Fractions in toto
2.5.7 Genetic, Pharmacological and Related Manipulations Integrated with CET
2.5.8 Identification Based on Labeling
2.5.9 Conclusions
Acknowledgments
REFERENCES
2.6 Visualizing Sub-cellular Organization Using Soft X-ray Tomography
Glossary
2.6.1 Introduction
2.6.2 Soft X-Ray Microscopy
2.6.3 Soft X-Ray Tomography: Theory
2.6.4 Soft X-Ray Tomography: Practice
2.6.5 Application of Soft X-Ray Tomography in Cell Biology
2.6.6 Localizing Molecules Using Correlated Light and X-Ray Microscopy
2.6.7 Summary and Future Prospects
REFERENCES
2.7 Atomic Force Microscopy
2.7.1 Cell Sample Preparation Methods
2.7.2 Atomic Force Microscopy Imaging
2.7.3 Molecular Recognition Force Spectroscopy
2.7.4 Recognition Imaging
2.7.5 Fluorescence Guided Molecular Force Spectroscopy and Combined Fluorescent/Simultaneous Topography and Recognition Imaging
REFERENCES
2.8 Super-Resolution Near-Field Optical Microscopy
Glossary
2.8.1 Optical Microscopy Beyond the Diffraction Limit of Light
2.8.2 The Near-Field Concept
2.8.3 Technical Implementation
2.8.4 Applications on Cellular Structures
2.8.5 Future Directions
2.8.6 Summary
REFERENCES
2.9 CARS Microscopy
2.9.1 Label-Free Optical Microscopy
2.9.2 Theoretical Basics of Coherent Anti-Stokes Raman Scattering
2.9.3 CARS Microscopy Excitation Geometries
2.9.4 Excitation Schemes for CARS Microscopy
2.9.5 Applications of CARS Microscopy
2.9.6 Outlook
REFERENCES
Elucidating Cellular Dynamics
2.10 Quantitative Fluorescent Speckle Microscopy
2.10.1 Introduction
2.10.2 What Is a Speckle and How Is It Formed?
2.10.3 Practical Requirements for Speckle Imaging
2.10.4 Algorithms for Image Analysis
2.10.5 Applications of FSM in Cell Biological Experiments
2.10.6 Conclusions
REFERENCES
2.11 Fluorescence Correlation Spectroscopy
Glossary
2.11.1 Introduction
2.11.2 Basic Principles of FCS
2.11.3 The Correlation Function
2.11.4 Extending Correlation Functions
2.11.5 Theoretical Approaches
2.11.6 Practical Aspects
2.11.7 Artifacts
2.11.8 Advanced FCS Techniques
2.11.9 Applications
2.11.10 Outlook
REFERENCES
2.12 Image Correlation Spectroscopy
2.12.1 Introduction
2.12.2 Principles and Theory of Image Correlation Spectroscopy
2.12.3 Variants of ICS
2.12.4 Experimental Considerations for ICS
2.12.5 Conclusion
REFERENCES
2.13 The Basics and Potential of Single-Molecule Tracking in Cellular Biophysics
2.13.1 Introduction
2.13.2 Single-Molecule Detection
2.13.3 Analysis of Single-Molecule Data
2.13.4 Applications
2.13.5 Conclusion
Acknowledgments
REFERENCES
Volume 3 The Folding of Proteins and Nucleic Acids
Protein Folding
3.1 Combining Simulation and Experiment to Map Protein Folding
Glossary
3.1.1 Introduction
3.1.2 Case Studies
3.1.3 Conclusions
REFERENCES
Globular Proteins
3.2 Energetics of Protein Folding
3.2.1 Introduction
3.2.2 Hydrophobic Effect
3.2.3 Hydrogen Bond
3.2.4 Electrostatic Interaction
3.2.5 Conformational Entropy
3.2.6 Strategies to Improve Protein Stability
Acknowledgment
REFERENCES
3.3 Fast Events in Protein Folding
3.3.1 Introduction
3.3.2 Simulating the Fast Events
3.3.3 Capturing the Fast Events Experimentally
3.3.4 An Archetypal Ultrafast Folding Protein: BdpA
3.3.5 Fast Folding Measurements of BdpA
3.3.6 Comparison of Experiments with Simulations
Acknowledgments
REFERENCES
3.4 Intermediates in Protein Folding
Glossary
3.4.1 Perspective
3.4.2 Equilibrium Intermediates
3.4.3 Kinetic Intermediates
3.4.4 Development of Quaternary Structure
3.4.5 Biological Significance
Acknowledgments
REFERENCES
3.5 Characterization of the Denatured State
Glossary
3.5.1 Introduction and Historical Perspective
3.5.2 Theoretical Approaches to Characterizing the DSE
3.5.3 Structural Methods for Analyzing the DSE
3.5.4 Thermodynamic Characterization of the DSE
3.5.5 Kinetics of Contact Formation in the DSE
3.5.6 Summary and Perspectives
REFERENCES
3.6 Single-Molecule Spectroscopy of Protein Folding
Glossary
3.6.1 Introduction
3.6.2 History and Principles of Single-Molecule Detection
3.6.3 Kinetics: From Ensembles to single-Molecules
3.6.4 Correlation Analysis
3.6.5 Single-Molecule Förster Resonance Energy Transfer
3.6.6 Experimental Aspects
3.6.7 Single-Molecule Spectroscopy of Protein Folding
3.6.8 Current Developments and Future Directions
3.6.9 Conclusion
Acknowledgments
REFERENCES
3.7 Simulation Studies of Force-Induced Unfolding
Glossary
3.7.1 Introduction
3.7.2 Force Probe Experiments and Their Interpretation
3.7.3 Mechanical Unfolding of Single Domain Proteins
3.7.4 Conclusions and Perspectives
Acknowledgments
REFERENCES
3.8 Protein and Nucleic Acid Folding: Domain Swapping in Proteins
Glossary
3.8.1 Introduction
3.8.2 General Aspects
3.8.3 Instructive Examples and Biological Implications
3.8.4 Conclusions
Acknowledgments
REFERENCES
3.9 Intrinsically Disordered Proteins
Glossary
3.9.1 Introduction
3.9.2 Structural Properties and Conformational Behavior of IDPs and IDPRs
3.9.3 Functional Repertoire of IDPs
3.9.4 Methods for Structural Characterization of IDPs
Acknowledgments
REFERENCES
3.10 Chaperones and Protein Folding
Glossary
3.10.1 Hsp70 Chaperones
3.10.2 Chaperonin Ring Assemblies
3.10.3 Small Heat Shock Proteins
3.10.4 Hsp90 Chaperones
REFERENCES
3.11 Protein Switches
3.11.1 Introduction
3.11.2 Engineered Switches
3.11.3 Synthetic Polymer–Protein Hybrids
3.11.4 Conclusions
Acknowledgments
REFERENCES
Repeat/Non-Globular Proteins
3.12 The Folding of Repeat Proteins
3.12.1 Repeat Proteins: Simplified Frameworks in which to Deconstruct Protein Folding
3.12.2 Equilibrium Stability of Repeat Proteins
3.12.3 Linear Statistical Mechanics Models to Describe the Stability of Repeat Proteins
3.12.4 Exploring the Presence of Partially Unfolded Species at the Equilibrium: Ising Model Predictions
3.12.5 The Basis and Limits of Cooperativity in Repeat Proteins
3.12.6 Unfolding Kinetics of Repeat Proteins
3.12.7 Denatured State in Repeat Proteins
3.12.8 Repeat Protein Folding: Roles in the Regulation of Biological Function
3.12.9 Conclusions
REFERENCES
Membrane Proteins
3.13 The Membrane Factor: Biophysical Studies of Alpha Helical Transmembrane Protein Folding
3.13.1 Introduction and Membrane Complexity
3.13.2 Solubilizing Systems and Refolding Methods
3.13.3 Folding Kinetics
3.13.4 Comparing Membrane and Water-Soluble Protein Folding
3.13.5 Co-translational Folding and Membrane Integration
3.13.6 Conclusions
REFERENCES
Nucleic Acid Folding
3.14 Effect of Protein Binding on RNA Folding
Glossary
3.14.1 Introduction
3.14.2 Why Does RNA Need Protein?
3.14.3 Protein-Assisted RNA Folding in the Ribosome
3.14.4 DExD/H Helicases and RNA Folding
3.14.5 Proteins That Fold Group I Introns
3.14.6 Summary
REFERENCES
Volume 4 Molecular Motors and Motility
4.1 Introduction
REFERENCES
General Theoretical Considerations
4.2 Microscopic Reversibility and Free-Energy Transduction by Molecular Motors and Pumps
Glossary
4.2.1 Introduction – Molecular Motors at and Away from Equilibrium
4.2.2 Microscopic Reversibility and Ligand Binding to Myoglobin
4.2.3 Cycles of Molecular Machines
4.2.4 Molecular Machines in a Thermal Environment
4.2.5 How Does the Chemical Reaction Drive Conformational Cycling?
4.2.6 A Two-Headed Motor that Walks Down a Track
4.2.7 Microscopic Reversibility and Dynamic Disorder
4.2.8 Conclusion
REFERENCES
Actin
4.3 Structure and Dynamic States of Actin Filaments
Glossary
4.3.1 Introduction
4.3.2 Bacterial Actin Homologs
4.3.3 Polymerization
4.3.4 Actin in Muscle
4.3.5 Development of an F-actin Model
4.3.6 Variable Twist in F-Actin
4.3.7 Variable Tilt in F-Actin
4.3.8 Allostery and Cooperativity
4.3.9 Higher Order Structures
REFERENCES
4.4 Actin Filament Nucleation and Elongation
4.4.1 Introduction
4.4.2 Biochemical Bases of Actin Polymerization
4.4.3 Actin Filament Nucleators
4.4.4 Formins
4.4.5 The W Domain and Actin Filament Nucleation
4.4.6 Tandem W Domain-Based Filament Nucleators
4.4.7 Role of Oligomerization on the Activities of Filament Nucleators
4.4.8 Filament Nucleation by NPFs-Arp2/3 Complex
4.4.9 Lmod and the Nucleation of Actin Filaments in Muscle Cells
4.4.10 Ena/VASP Proteins as Dedicated Elongation Factors
4.4.11 Profilin and the Pro-Rich Regions of Nucleation and Elongation Factors
4.4.12 Concluding Remarks
Acknowledgments
Appendix A Supporting Materials
Appendix A Supporting materials
REFERENCES
4.5 Mechanical Properties of Actin Networks
4.5.1 Introduction
4.5.2 Rheology
4.5.3 Reconstituted Crosslinked Actin Networks
4.5.4 Reconstituted Contractile F-Actin Networks
4.5.5 Reconstituted Protrusive F-Actin Networks
4.5.6 Summary and Outlook
Acknowledgments
REFERENCES
Microtubles
4.6 Tubulin and Microtubule Structure: Mechanistic Insights into Dynamic Instability and Its Biological Relevance
Glossary
4.6.1 Introduction to Microtubules and Dynamic Instability
4.6.2 Tubulin Structure
4.6.3 Microtubule Lattice Structure
4.6.4 Alternative Conformational States of Tubulin
4.6.5 Biological Roles of Structural Intermediates in Microtubule Assembly and Disassembly
REFERENCES
4.7 Force Generation by Dynamic Microtubule Polymers
Glossary
4.7.1 Microtubules Are Ubiquitous Cytoskeletal Polymers, Essential for Cell Health and Viability
4.7.2 Growing MTs Can Push
4.7.3 Shortening MTs Can Pull on a Load in at Least Two Ways
4.7.4 Theoretical and Experimental Analysis of an MT Depolymerization Motor
4.7.5 Molecular Devices to Couple MT Depolymerization to Processive Cargo Motion
4.7.6 Summary
REFERENCES
Myosin
4.8 Myosin Motors: Structural Aspects and Functionality
4.8.1 Introduction
4.8.2 Structural Features of the Myosin Motor Domain
4.8.3 Allosteric Communication
4.8.4 Summary and Conclusions
REFERENCES
4.9 Myosin Motors: Kinetics of Myosin
Glossary
4.9.1 Introduction
4.9.2 Early Studies of Myosin
4.9.3 The Paradox
4.9.4 Kinetic Measurements
4.9.5 The Kinetic Pathway is Conserved for Most Characterized Myosins
4.9.6 ADP Release and Force Sensitivity
4.9.7 Kinetic Diversity of the Myosin Family
4.9.8 Summary
Acknowledgments
REFERENCES
4.10 Single Molecule Fluorescence Techniques for Myosin
Glossary
4.10.1 Introduction
4.10.2 A Description of the Major Techniques that Use Fluorescence to Study Single Molecules
4.10.3 Early Single Molecule and Polarization Studies
4.10.4 Some Myosins Move Processively Along Actin
4.10.5 Single Molecule Fluorescence Studies of Myosin-5a
4.10.6 Regulation of Processive Myosins
4.10.7 Unconventional Myosins – Single-Headed or Double-Headed?
4.10.8 Visualizing Single Molecules in Cells
4.10.9 Conclusions
REFERENCES
Muscle
4.11 Cell-Based Studies of the Molecular Mechanism of Muscle Contraction
Glossary
4.11.1 Introduction
4.11.2 The Sarcomere: Structural and Functional Unit of Striated Muscle
4.11.3 Structure of Thick and Thin Filaments
4.11.4 The Isometric Twitch: Unitary Response of an Intact Muscle Cell
4.11.5 Skinned Muscle Fibers
4.11.6 Muscle Mechanics and Energetics in the Steady State
4.11.7 The Cross-Bridge Paradigm: Cycles and Strokes
4.11.8 Myosin as a Motor Protein: A.F. Huxley′s (1957) Model
4.11.9 Stiffness of Sarcomeres, Filaments and Myosin Motors
4.11.10 Inside the Cross-Bridge Cycle: Mechanical Kinetics
4.11.11 Mechano-Chemical Coupling
4.11.12 Methods for Studying Molecular Structural Dynamics in Muscle
4.11.13 Structure of Myosin Filaments and Myosin Head Conformations in Reference States
4.11.14 Structure of Myosin Filaments and Myosin Head Conformations during Isometric Contraction
4.11.15 Mechano-Structural Coupling and its Kinetics
4.11.16 Structural Dynamics of Muscle Regulation
4.11.17 Resistance to Stretch: Muscle as a Brake
4.11.18 Summary and Perspective
REFERENCES
4.12 Spectroscopic Probes of Muscle Proteins
Glossary
4.12.1 Introduction
4.12.2 Case Studies
4.12.3 Summary
REFERENCES
4.13 Thin Filament Regulation
Glossary
4.13.1 Introduction
4.13.2 The Players Tropomyosin and Troponin
4.13.3 Structural Changes within the Regulated Actin Filaments
4.13.4 Biochemical Studies of the Thin Filament Regulation
4.13.5 Co-operativity
4.13.6 The Myosin ATPase
4.13.7 In vitro Motility Assays and Regulation
4.13.8 Fibers and Myofibrils
REFERENCES
4.14 Smooth Muscle and Myosin Regulation
4.14.1 Background
4.14.2 Folded-to-Extended Conformational Transition
4.14.3 Mutational Studies of the RLC
4.14.4 Rod Mutations
4.14.5 Motor Domain Mutations
4.14.6 Structural Basis of Regulation: The Lever Arm
4.14.7 Structural Basis of Regulation: Asymmetric Head-Head Interactions
4.14.8 Features of the Rod in the 10S State
4.14.9 Head-Head Interactions in Striated Muscle Myosins
4.14.10 What Happens Upon Activation?
4.14.11 Properties of Myosin with One of its Two Heads Phosphorylated
4.14.12 Does the Folded Form of Smooth Muscle Myosin Exist In Vivo?
4.14.13 Unique Features of Smooth Muscle Myosin
4.14.14 Unique Features of Smooth Muscle
4.14.15 Smooth Muscle Isoforms
4.14.16 Smooth Muscle Myosin Mutations Implicated in Disease
4.14.17 Future Goals
Acknowledgments
REFERENCES
Non-Muscle Motility
4.15 Intracellular Transport: Relating Single-Molecule Properties to In Vivo Function
Glossary
4.15.1 Overview
4.15.2 An Introduction to the Families of Molecular Motors
4.15.3 Single-Molecule Properties of the Molecular Motors
4.15.4 From Single Motor Function to In Vivo Transport: The Issues
4.15.5 Summary
REFERENCES
4.16 Mechanical Forces in Mitosis
Glossary
4.16.1 Introduction
4.16.2 Metaphase Spindle Organization and Dynamics
4.16.3 Molecular Origin of Forces
4.16.4 Mapping Forces within Spindles
4.16.5 Spindle Length Regulation
4.16.6 Mechanics of the Kinetochore–Microtubule Interface
Acknowledgements
REFERENCES
Kinesin
4.17 Kinesin Structure and Biochemistry
Glossary
4.17.1 Introduction
4.17.2 Processive KinN Kinesins
4.17.3 Nonmotile Kinesin-10 NOD
4.17.4 Perspectives
Acknowledgments
REFERENCES
4.18 Kinesin Single-Molecule Mechanics
Glossary
4.18.1 Introduction
4.18.2 Structure
4.18.3 Kinesin Motility
4.18.4 Mechanochemical Cycle
4.18.5 Conclusion and Future Directions
REFERENCES
Dynein
4.19 Cytoplasmic Dynein: Its ATPase Cycle and ATPase-dependent Structural Changes
Glossary
4.19.1 Cytoplasmic Dynein is a Mechanochemical Enzyme Belonging to the AAA+Superfamily
4.19.2 The Modular Structure of the Dynein Heavy Chain
4.19.3 The Minimal Motor Domain of Cytoplasmic Dynein
4.19.4 The AAA Ring as the ATPase Module
4.19.5 The Linker as the Powerstroke Module
4.19.6 The Stalk as the Switching Module for MT Attachment/Detachment
4.19.7 The Mechanochemical Properties of the Motor Domain
4.19.8 Future Perspectives
REFERENCES
4.20 Axonemal Motility
Glossary
4.20.1 Introduction
4.20.2 The Axoneme
4.20.3 Axonemal Dyneins
4.20.4 Conclusion
Acknowledgments
REFERENCES
Nucleic Acid Motors
4.21 The Ribosome
Glossary
4.21.1 Introduction
4.21.2 Ribosome Composition and Structure
4.21.3 The Translation Cycle
4.21.4 Biophysical Approaches to Elucidating the Mechanisms of Individual Steps of the Translation Cycle
4.21.5 The Overall Rhythm of Protein Synthesis
4.21.6 Is the Ribosome a Biomolecular Brownian Motor?
4.21.7 Overall Summary
4.21.8 A Note on Translation Videos
REFERENCES
4.22 Viral DNA Packaging Motors
Glossary
4.22.1 Packaging in the Double-Stranded DNA Bacteriophages
4.22.2 What are the Components and Organization of the Packaging Complex?
4.22.3 How is Packaging Initiated?
4.22.4 How is the DNA Translocated?
4.22.5 What are the Organization and Physics of the Genome during and after Packaging?
4.22.6 How is Packaging Terminated?
4.22.7 Conclusions and Future Directions
REFERENCES
Volume 5 Membranes
Volume Introduction
5.1 Biophysics of Membranes
REFERENCES
Lipid Bilayers
5.2 Lipid Bilayer Structure
Glossary
5.2.1 General Concepts
5.2.2 Lipids and Water (Hydrophobicity)
5.2.3 Structural Parameters (Geometry)
5.2.4 Molecular Fluctuations within Bilayers
5.2.5 Structural Deformations
5.2.6 Bilayer Undulations
5.2.7 Appendix: X-Ray and Neutron Scattering of Lipid Bilayers
REFERENCES
5.3 Membrane Domains and Their Relevance to the Organization of Biological Membranes
Glossary
5.3.1 Historical Perspectives of Membrane Domains
5.3.2 Lateral Organization of Lipid Bilayers: Model Systems and Experimental Techniques
5.3.3 Direct Visualization of Lipid Domains
5.3.4 Specialized Biological Membranes: Pulmonary Surfactant and Skin Lipids
5.3.5 Membrane Domains in Biological Membranes and Their Relation to the ‘Raft’ Hypothesis
5.3.6 Challenges and Future Perspectives
Acknowledgments
REFERENCES
5.4 Atomic Force Microscopy and Fluorescence Microscopy of Lipid Bilayers
Glossary
5.4.1 Fluorescence and Atomic Force Microscopy
5.4.2 Imaging Lipid Phase Behavior
5.4.3 Imaging Supported Lipid Bilayer Formation
5.4.4 Imaging Curvature Effects in Lipid Bilayers
5.4.5 Measurements of Lipid Forces by AFM
REFERENCES
5.5 Detergent Interactions with Lipid Bilayers and Membrane Proteins
5.5.1 Scope and Introduction
5.5.2 Self-Association
5.5.3 Stages and Phases of a Lipid/Detergent System, an Overview
5.5.4 Membrane Partitioning (Stage I)
5.5.5 Sublytic Membrane Perturbation (Stage I)
5.5.6 Solubilization of Membranes via Bilayer/Micelle Coexistence (Stage II)
5.5.7 Lipid–Detergent Micelles (Stage III)
5.5.8 Detergents in Membrane Protein Studies
Acknowledgments
REFERENCES
Membrane Proteins
5.6 Atomic Force Microscopy and Electron Microscopy of Membrane Proteins
Glossary
5.6.1 Introduction
5.6.2 Electron-crystallography
5.6.3 Atomic Force Microscopy
5.6.4 Single Molecule Force Spectroscopy
5.6.5 Perspectives
Acknowledgments
REFERENCES
5.7 Solution NMR Spectroscopy of Integral Membrane Proteins
Glossary
5.7.1 Introduction
5.7.2 Preparation of Membrane Protein Samples for Solution NMR Studies
5.7.3 Solution NMR Techniques for Integral Membrane Proteins
5.7.4 Solution NMR Studies of Integral Membrane Proteins
5.7.5 Discussion and Outlook
REFERENCES
5.8 Structure and Folding of Outer Membrane Proteins
5.8.1 Introduction
5.8.2 Outer Membrane Protein Structures
5.8.3 Outer Membrane Protein Folding
Acknowledgments
REFERENCES
5.9 Pore-Forming Toxins
5.9.1 Introduction
5.9.2 General Mode of Action of Pore Forming Toxins
5.9.3 Structural Classification of Pore-Forming Toxins
5.9.4 Methodological Approaches to Understanding Pore-Forming Toxins
5.9.5 Pore-Forming Proteins as Tools in Cell Biology, Immunology, and Bioengineering
REFERENCES
Protein Interactions With Membranes
5.10 Interactions of Antimicrobial Peptides with Lipid Bilayers
Glossary
5.10.1 Introduction
5.10.2 Types of Antimicrobial Peptides
5.10.3 How Sequence Determines Structure and Activity
5.10.4 Kinetics of Membrane Disruption
5.10.5 Thermodynamics and Kinetics of Binding to Membranes
5.10.6 Membrane Elasticity and Peptide Activity
5.10.7 Membrane Disruption by Antimicrobial Peptides
5.10.8 Conclusion
Acknowledgment
REFERENCES
5.11 Membrane Recruitment of Signaling Domains
Glossary
5.11.1 Introduction
5.11.2 Phospholipid Bilayers and Membrane Binding Domains
5.11.3 Mechanisms of Membrane Recruitment
5.11.4 In Vitro and In Silico Analyses of Membrane Recruitment
5.11.5 Cell-Based Analyses of Membrane Recruitment
REFERENCES
5.12 Membrane Protein–Lipid Match and Mismatch
5.12.1 Introduction
5.12.2 The Principle of Hydrophobic Matching and Its Relation to Trans-Bilayer Structure
5.12.3 Lipid-Protein Interactions in Membranes by Hydrophobic Matching
5.12.4 Experimental Evidence for Hydrophobic Matching being in Control of Protein Function
5.12.5 Membrane Organization by Hydrophobic Matching
Acknowledgments
REFERENCES
5.13 Supported Membranes – Structure and Interactions
5.13.1 Introduction – Membranes as Assemblies of Lipids and Proteins
5.13.2 Biogenesis of Membrane Proteins
5.13.3 Fabrication of Biomembrane Models: Supported Membranes
5.13.4 Supported Membranes: Functionalization with Proteins
5.13.5 Lateral Diffusion in Two-Dimensional Membranes: Continuum Approach
5.13.6 Lateral Diffusion in Two-Dimensional Membranes: Free Volume Approach
5.13.7 Lateral Diffusion of Proteins in Supported Membranes
5.13.8 Contact Between Supported Membranes and Solid Substrates
5.13.9 Polymer Interlayers at Membrane-Substrate Contacts
5.13.10 Modulation of Membrane-Substrate Contacts with Polymers
5.13.11 Native Membranes on Polymer Supports
Acknowledgments
REFERENCES
Membrane Fusion
5.14 The Biophysics of Membrane Fusion
5.14.1 How Can We Study Membrane Fusion?
5.14.2 Do Membranes Spontaneously Fuse?
5.14.3 Is the Interior of The Fusion Pore Made of Protein or Lipid?
5.14.4 Why Is Synaptic Vesicle Fusion So Fast?
5.14.5 Why Is PtdIns-4,5-P2 Needed for Exocytotic Fusion?
5.14.6 Biophysical Approaches to Understanding Viral Fusion Machines
5.14.7 Questions Arising from Structural Studies of SNARE Proteins
5.14.8 Single Molecule Studies of Membrane Fusion
5.14.9 What Can Membrane Fission Tell Us About Membrane Fusion?
5.14.10 Perspective
Acknowledgments
REFERENCES
5.15 Mechanisms of Enveloped Virus Entry by Membrane Fusion
Glossary
5.15.1 Introduction
5.15.2 Structure and Classification of Viral Envelope Glycoproteins
5.15.3 Regulation and Control of the Fusion Reaction
5.15.4 Diverse Viral Proteins Evolved to Mediate Membrane Merger through the Same Principal Mechanism
5.15.5 Detection and Quantification of Viral Fusion
5.15.6 Functional Characterization of Viral Fusion Intermediates: Filling the Blanks
5.15.7 Roles of the Transmembrane Domain and Cytoplasmic Tail
5.15.8 Stoichiometry and Cooperativity of Viral Fusion
5.15.9 Viral Entry Pathways and Host Cell Factors
5.15.10 Conclusion
Acknowledgments
REFERENCES
Membrane Dynamics
5.16 Computer Simulation of Membrane Dynamics
5.16.1 Introduction
5.16.2 Methods
5.16.3 Example Applications
5.16.4 Outlook
Acknowledgments
REFERENCES
5.17 Single Molecule Measurements in Membranes
Glossary
5.17.1 Introduction
5.17.2 Single Molecule Detection in General
5.17.3 Single Molecule Detection in Biomembranes
5.17.4 Model and Biomembrane Systems
5.17.5 Labels for Single Molecule Studies in Membranes
5.17.6 Biomembranes Studied at the Single Molecule Level
5.17.7 Conclusion
Acknowledgments
REFERENCES
Volume 6 Channels
6.1 Channel Proteins – An Introduction
Glossary
REFERENCES
6.2 Structure-Function Correlates of Glutamate-Gated Ion Channels
6.2.1 Structure of Glutamate-Gated Ion Channels
6.2.2 Glutamate Receptor Activation and Modulation
6.2.3 Glutamate Receptor Gating
6.2.4 Glutamate Receptor Permeation
Acknowledgments
REFERENCES
6.3 Gating Dynamics of the Potassium Channel Pore
Glossary
6.3.1 Introduction
6.3.2 Diverse and Ubiquitous K Channels
6.3.3 The Structure of Ion Channels
6.3.4 Gating Kinetics
6.3.5 Energetics of Pore Gating
6.3.6 Single Molecule Dynamics
6.3.7 Structural Dynamics of Gating at the Single Molecule Level
6.3.8 Structural Dynamics of the KcsA Channel
6.3.9 Intramolecular Wave Propagation
6.3.10 Conclusion
REFERENCES
6.4 Biophysics of TRP Channels
6.4.1 Introduction
6.4.2 Structural Features of TRP Channels
6.4.3 Voltage and Ca2+ Dependence of TRP Channels
6.4.4 Activation and Regulation Mechanisms of TRP Channels
6.4.5 TRP and Lipids
6.4.6 Physiological Implications
6.4.7 TRP Integrative Function
6.4.8 Concluding Remarks
REFERENCES
6.5 Mechanosensory Transduction
6.5.1 Introduction
6.5.2 Mechanotransduction in Microbial Cells
6.5.3 Mechanosensory Transduction in Plants
6.5.4 Diversity of MS Channels and Receptors in Animal Cells
6.5.5 Mechanosensitivity in the Nervous System: Physiological and Pathological Significance of MS Channels
6.5.6 Mechanosensation in Cochlea
6.5.7 Mechanoreception in Peripheral Tissue
6.5.8 Conclusions and Outlook
REFERENCES
6.6 Structures and Mechanisms in Chloride Channels
6.6.1 Introduction
6.6.2 Structures and Mechanisms of CLC Channels/Transporters
6.6.3 Structures and Mechanisms of CFTR Chloride Channels
Acknowledgments
REFERENCES
6.7 Biophysics of Ceramide Channels
Glossary
6.7.1 Introduction to Ceramide and Its Role in Apoptosis
6.7.2 Ceramide Channel Formation in Phospholipid Membranes
6.7.3 Ceramide Channel Formation in Mitochondrial Membranes
6.7.4 Molecular Structure of the Ceramide Channel
6.7.5 Results from Molecular Dynamic Simulations
6.7.6 Regulation by Anti-Apoptotic Proteins
6.7.7 Perspective and New Questions
Acknowledgment
REFERENCES
6.8 Voltage Gated Proton Channels
6.8.1 Research History of Voltage-Gated Proton Channel
6.8.2 Basics of Proton Transfer in Biological Environment and Lessons from Several Proton-Transporting Proteins
6.8.3 Properties of Native Hv Channels
6.8.4 Molecular Structure of Voltage-Gated Proton Channels
6.8.5 Mechanisms of Hv Channel Proton Permeation and Gating
6.8.6 Hv Channel Activities in Physiological Contexts
REFERENCES
6.9 STIM1-ORAI1 Store-Operated Calcium Channels
6.9.1 STIM1-ORAI1 Store-Operated Calcium Current
6.9.2 CRAC Current
6.9.3 Recombinant STIM1 and ORAI1
6.9.4 ORAI1 – The Plasma Membrane Calcium Channel
6.9.5 STIM1 – The ER Calcium Sensor
6.9.6 STIM1 and ORAI1 – Channel Gating
6.9.7 Conclusion
Acknowledgment
REFERENCES
6.10 Structure–Function Correlates in Plant Ion Channels
Glossary
6.10.1 Introduction
6.10.2 Topology of K+ Channels
6.10.3 Selectivity Filter of K+ Channels and the HKT K+ Transporter
6.10.4 Channel or Transporter: What Determines Protein Function?
6.10.5 Integration of K+ Channels into the Membrane
6.10.6 Gating of Plant K+ Channels
6.10.7 Assembly of Plant K+ Channels: Diversity through Heteromerization
6.10.8 Outlook
REFERENCES
Volume 7 Cell Biophysics
7.1 Introduction
7.2 Biophysics of Cell-Matrix Adhesion
Glossary
7.2.1 Cell Adhesion in Multicellular Organisms
7.2.2 Cell-ECM Adhesion Through Focal Adhesions
7.2.3 Response of Cells to Mechanical Forces Through Focal Adhesions
7.2.4 Integrin Family and Affinity Regulation
7.2.5 Measuring Force Regulation of Integrin/Ligand Dissociation
7.2.6 Lifetime–Force Relationship of FNIII7–10/α5β1-Fc Interaction
7.2.7 Biological Relevance of Integrin/Ligand Catch Bonds
7.2.8 Closing Remarks
REFERENCES
7.3 Biophysics of Selectin-Mediated Cell Adhesion
Glossary
7.3.1 Introduction
7.3.2 Two-dimensional (2-D) Receptor–Ligand Binding Kinetics
7.3.3 Selectin–Ligand Dissociation: Slip Bond Kinetic Parameters
7.3.4 Selectin–Ligand Bonds Exhibit Catch Bond Behavior
7.3.5 Selectin-Mediated Cell Adhesion in Shear Flow
7.3.6 Conclusion
Acknowledgments
REFERENCES
7.4 Biophysics of Cadherin-Mediated Cell–Cell Adhesion
Glossary
7.4.1 Introduction
7.4.2 Cadherin Junction as a Dynamic Mechanical Integrator
7.4.3 Molecular Interactions at Cadherin Junctions
7.4.4 Generation of Forces at Cadherin Junctions
7.4.5 Conclusions
Acknowledgements
REFERENCES
7.5 Understanding How Dividing Cells Change Shape
Glossary
7.5.1 Introduction
7.5.2 Physical Parameters
7.5.3 The Mechanical Parts List
7.5.4 Mechanical Features of the Cortical Cytoskeletal Network
7.5.5 Dissecting Mechanics Across Variable Timescales and Length Scales
7.5.6 Mechanical Properties of Cytokinesis: Active vs. Passive
7.5.7 Mechanical Interplay Between Myosin II and Actin Crosslinkers
7.5.8 Role of Cell Surface Interactions
7.5.9 Mechanosensing and Mechanical Feedback
7.5.10 Biochemical-Mechanical Feedback Loops
7.5.11 Cleavage Furrow Ingression Through Three Mechanical Transitions
7.5.12 Cylinder-Thinning Model
7.5.13 Contractile Rings: The Schizosaccharomyces pombe Case
7.5.14 Comparisons Between Systems
7.5.15 Conclusion
Acknowledgments
REFERENCES
7.6 Biophysics of Bacterial Cell Growth and Division
7.6.1 Introduction
7.6.2 Bacterial Cell Wall and the Physics of Morphogenesis
7.6.3 Physical Properties of FtsZ and Formation of the Z-ring
7.6.4 Z-ring Force Generation Mechanisms
7.6.5 Conclusions and Perspectives
Acknowledgments
REFERENCES
7.7 Biophysics of Three-Dimensional Cell Motility
Glossary
7.7.1 Introduction
7.7.2 Extracellular Matrix
7.7.3 Components of Cell Motility
7.7.4 Other Mechanisms of Cell Motility in Three Dimensions
7.7.5 Computational Models of Cells Moving in Three Dimensions
7.7.6 Conclusions
REFERENCES
7.8 Biophysics of Molecular Cell Mechanics
Glossary
7.8.1 Introduction and Motivation
7.8.2 Basic Concepts of Molecular and Cellular Mechanics
7.8.3 Particle Tracking Microrheology
7.8.4 Microrheology of Live Cells
Acknowledgments
REFERENCES
7.9 Biophysics of Nuclear Organization and Dynamics
Glossary
7.9.1 Introduction and Motivation
7.9.2 Nuclear Envelope
7.9.3 Lamina Nucleoskeleton
7.9.4 Nucleoplasm and Genome
7.9.5 Conclusions and Future Challenges
Acknowledgment
REFERENCES
7.10 Cell-Extracellular Matrix Mechanobiology in Cancer
Glossary
7.10.1 Introduction
7.10.2 Cellular Mechanotransdution: Background and Overview
7.10.3 Mechanobiology of Tumor Initiation
7.10.4 Mechanobiology of Angiogenesis
7.10.5 Mechanobiology of Tumor Invasion and Metastasis
7.10.6 Case Study: Mechanobiology of Glioblastoma Multiforme
7.10.7 Mechanobiological Signaling Pathways as Therapeutic Targets in Cancer
7.10.8 Conclusions and Future Directions
Acknowledgments
REFERENCES
7.11 Biomechanics of Cell Motility
7.11.1 Introduction
7.11.2 Cellular Movements in Fluid
7.11.3 Gliding and Crawling on a Surface
7.11.4 Conclusions
Acknowledgments
REFERENCES
7.12 Biophysics of Cell Developmental Processes: A Lasercutter's Perspective
Glossary
7.12.1 Laser-Based Targeted Elimination of Subcellular Structures and Entire Cells
7.12.2 Laser Ablation for Active Cell and Tissue Mechanics
7.12.3 Conclusion
REFERENCES
7.13 Bacterial Organization in Space and Time
Glossary
7.13.1 Introduction
7.13.2 Organization Principles
7.13.3 The Bacterial Cytoskeleton
7.13.4 Positioning The Z-Ring
7.13.5 Polar Protein Localization
7.13.6 Chromosome segregation and protein distributions
7.13.7 Temporal Organization
7.13.8 Concluding remarks
REFERENCES
Volume 8 Bioenergetics
8.1 Ion Electrochemical Gradients, Roles and Measurements
8.1.1 Introduction to Electrochemical Gradients
8.1.2 Mechanisms of Generating Electrochemical Gradients
8.1.3 Roles of Electrochemical Gradients
8.1.4 Measuring Electrochemical Gradients
REFERENCES
8.2 Structure-Function Relationships in P-Type ATPases
Glossary
8.2.1 Introduction
8.2.2 SERCA1a Domain Structures
8.2.3 Towards a Structural Description of the SERCA1a Transport Cycle
8.2.4 Regulatory Aspects of the Pumping Mechanism
8.2.5 Structure of Other P-Type Atpases
REFERENCES
8.3 Rotational Catalysis by F1-ATPase
Glossary
8.3.1 Introduction
8.3.2 Rotation of F1
8.3.3 Chemo-Mechanical Coupling
8.3.4 Energetics of Coupling
8.3.5 Structural Basis of Rotation
Acknowledgments
REFERENCES
8.4 The Rotary Bacterial Flagellar Motor
8.4.1 Introduction
8.4.2 Propeller and Universal Joint
8.4.3 Energy Transduction
8.4.4 Mechanism of Torque Generation
8.4.5 Control of Motor Rotation
8.4.6 Outlook
REFERENCES
8.5 Electron Transfer Chains: Structures, Mechanisms and Energy Coupling
Glossary
8.5.1 Introduction
8.5.2 Common Types of Electron Transfer Prosthetic Groups
8.5.3 Respiratory Connectors: Quinones, Cytochromes c, and Blue Copper Proteins
8.5.4 The Mitochondrial Electron Transfer Chain
8.5.5 Bacterial Electron Transfer Systems
Acknowledgement
REFERENCES
8.6 Light Capture in Photosynthesis
8.6.1 Introduction
8.6.2 Chromophore Pigments
8.6.3 Overview of the Mechanisms for Energy Transfer among Pigments
8.6.4 Methods of Measurement of Energy Transfer between Pigments
8.6.5 Structures and Energy Transfer Properties of Antenna Pigment-Protein Complexes
8.6.6 Synthetic Macromolecular Systems That Mimic Photosynthetic Light Harvesting
Acknowledgments
REFERENCES
8.7 The Structure-Function Relationships of Photosynthetic Reaction Centers
8.7.1 Introduction
8.7.2 Overview of Photosynthetic RCs
8.7.3 Structure and Mechanism of the RC of Purple Photosynthetic Bacteria
8.7.4 The RCs of Oxygenic Photosynthesis
8.7.5 Structure and Function of the Photosystem II RC of Oxygenic Photosynthesis
8.7.6 Structure and Function of the Photosystem I RC of Oxygenic Photosynthesis
8.7.7 Type I RCs of Green Sulfur Bacteria and Heliobacteria
8.7.8 Conclusions
REFERENCES
8.8 Molecular Aspects of the Translocation Process by ABC Proteins
Glossary
8.8.1 Introduction
8.8.2 Generic Aspects of Transbilayer Translocation Processes
8.8.3 Substrate Binding by ABC Proteins
8.8.4 Energy Transduction in ABC Transporters
8.8.5 Coupling Energy Production and Substrate Binding in ABC Transporters
8.8.6 Conclusion
REFERENCES
8.9 Structural and Mechanistic Aspects of Mitochondrial Transport Proteins
8.9.1 Introduction
8.9.2 Physiological Role of Mitochondrial Transport Proteins
8.9.3 Structure of the Mitochondrial Carriers
8.9.4 Substrate and Proton Binding Sites of Mitochondrial Transport Proteins
8.9.5 Mitochondrial Transport Proteins Function as Monomers
8.9.6 Proposed Transport Mechanism of Mitochondrial Transport Proteins
8.9.7 Properties of Mitochondrial Nucleotide Transport Proteins
8.9.8 Properties of Mitochondrial Keto Acid Transport Proteins
8.9.9 Properties of Mitochondrial Amino Acid Transport Proteins
8.9.10 Properties of Mitochondrial Inorganic Ion Transport Proteins
8.9.11 Properties of Mitochondrial Uncoupling Proteins and Orthologs
8.9.12 Properties of Mitochondrial Cofactor Transport Proteins
8.9.13 Mitochondrial Transport Proteins with Unknown Specificity
8.9.14 Perspectives
REFERENCES
8.10 Light Capture and Energy Transduction in Bacterial Rhodopsins and Related Proteins
8.10.1 Introduction
8.10.2 Structure and Structural Changes
8.10.3 The Chromophore and Absorption of Light
8.10.4 Pre-Proton Transfer Intermediates
8.10.5 Deprotonation of the Retinal Schiff Base and Proton Release
8.10.6 The Protonation Switch
8.10.7 Reprotonation of the Schiff Base, Retinal Reisomerization, and Proton Uptake
8.10.8 Large-Scale Conformational Changes
8.10.9 Mechanistic Schemes Based on Structural Results
8.10.10 Ion Specificity
8.10.11 Overall Energetics of the Pump
REFERENCES
8.11 Transporters and Co-transporters in Theory and Practice
Glossary
8.11.1 Introduction to the General Theory of Transporters
8.11.2 Enzyme versus Transport Kinetics
8.11.3 Cotransport Models
8.11.4 Serotonin Transporters
8.11.5 DATs
8.11.6 Chloride Channels and Transporters
8.11.7 Summary
Acknowledgment
REFERENCES
8.12 Membrane Proteins for Secondary Active Transport and their Molecular Mechanisms
8.12.1 Introduction
8.12.2 Bioenergetics of Membrane Transport
8.12.3 Classification of Transporters by their Amino Acid Sequences
8.12.4 Secondary Active Membrane Transport Proteins
8.12.5 The Major Facilitator Superfamily (MFS) is Related by Similarities of Amino Acid Sequences
8.12.6 The LeuT Superfamily Related by Similarity of Three-Dimensional Structures
8.12.7 The Mhp1 Protein and its Molecular Mechanism
8.12.8 The Na+/H+ Antiport Transport Protein
8.12.9 Reprise of the Alternating Access Concept of Transport
8.12.10 Concluding Remarks
Acknowledgments
REFERENCES
Volume 9 Simulation and Modelling
Volume Introduction
9.1 Theoretical Biophysics: A Cornerstone of Understanding in Modern Biology and Biomedicine
In Silico Approaches to Structures and Function of Cell Components and Their Aggregates
9.2 Coarse-Grained Methods: Theory
9.2.1 Introduction
9.2.2 Spatial Coarse Graining
9.2.3 Temporal Coarse Graining
REFERENCES
9.3 In Silico Coarse-Grained Approaches to Structural Dynamics and Function of Proteins and their Assemblies
9.3.1 Introduction: Protein Dynamics, Allostery and Function
9.3.2 Elastic Network Models: Theory and Methods
9.3.3 Applications to Allosteric Systems and Supramolecular Machines
9.3.4 Beyond Structural Dynamics: Extensions and Future Directions
Acknowledgment
REFERENCES
9.4 Coarse Grained Methods: Applications to Membranes
9.4.1 What Can We Learn from Coarse Grained Models of Lipid Bilayers?
9.4.2 How to Coarse Grain a Lipid Bilayer?
9.4.3 Learning from Examples
9.4.4 Prospects for Coarse Grained Lipid Models
Acknowledgments
REFERENCES
9.5 Dynamics of Very Large Systems: The Ribosome
Glossary
9.5.1 The Ribosome Synthesizes Proteins in all Organisms
9.5.2 The Ribosome is a Ribonucleoprotein Complex
9.5.3 Transfer RNA Molecules are Used by the Ribosome to Translate the Genetic Code
9.5.4 Protein Synthesis Occurs in Three Stages: Initiation, Elongation, and Termination
9.5.5 The Ribosome is Dynamic in Nature
9.5.6 Computational Studies of the Ribosome
9.5.7 Implications for the Free Energy Landscape of the Ribosome and Translation Energetics
REFERENCES
9.6 New Technologies for Molecular Dynamics Simulations
Glossary
9.6.1 Introduction
9.6.2 Scope
9.6.3 Anatomy of an MD Simulation
9.6.4 Speed
9.6.5 Force Field Accuracy
9.6.6 Analysis of Very Long Trajectories
9.6.7 Applications of Very Long MD Simulations
9.6.8 Conclusion
Acknowledgment
REFERENCES
Simulations of Molecular Mechanisms
9.7 Molecular Modeling and Simulations of Transporter Proteins – The Transmembrane Allosteric Machinery
Glossary
9.7.1 Background and Introduction
9.7.2 Structure-Function Information Deduced from the Sequence and Structural Alignments
9.7.3 Elements in Building Models and Simulation Systems
9.7.4 Molecular Simulations in the Mechanistic Studies
9.7.5 The Leading Role of Modeling and Simulations in Advancing Mechanistic Understanding of NSS Transport
9.7.6 Concluding Remarks
REFERENCES
9.8 Gene Protein Coupled Receptors
Glossary
9.8.1 Structure and Dynamics of GPCR Monomers
9.8.2 Structure and Dynamics of GPCR Dimers/Oligomers
Acknowledgments
REFERENCES
9.9 Quantum Mechanical Methods for Enzyme Modeling: Accurate Computation of Kinetic Isotope Effects
9.9.1 Introduction
9.9.2 Method
9.9.3 Illustrative Examples
9.9.4 Conclusion
Acknowledgments
REFERENCES
9.10 MNDO-PSDCI and the Analysis of the Photophysical Properties of Visual Chromophores and Retinal Proteins
Glossary
9.10.1 Introduction
9.10.2 Methods of Studying Electronically Excited States
9.10.3 Application of MNDO-PSDCI to Isolated Biological Molecules
9.10.4 Applications of MNDO-PSDCI to Protein-Bound Chromophores
9.10.5 Conclusions
REFERENCES
In Silico Approaches to Structure and Function of Cell Components and Their Assemblies
9.11 Molecular Electrostatics and Solvent Effects
Glossary
9.11.1 Introduction
9.11.2 Intracellular Water
9.11.3 Atomistic Representations of Water and Solutes
9.11.4 Continuum Description of Water Electrostatic Effects
9.11.5 Modeling of Hydrophobic and Hydrophilic Forces
9.11.6 pH-Dependent Electrostatic Properties in Proteins
9.11.7 Perspectives for the Future
Acknowledgments
REFERENCES
9.12 Interactions of the Cell Membrane with Integral Proteins
Glossary
9.12.1 Evidence for Role of Lipid Environment for Membrane Protein Function
9.12.2 Key Elements of Lipid-Protein Interactions
9.12.3 Framework for Quantitative Description of Lipid-Protein Interactions
9.12.4 Illustrative Applications
9.12.5 Concluding Remarks
Acknowledgments
REFERENCES
Modeling of Interaction Networks in the Cell
9.13 Theory and Mathematical Methods
9.13.1 Introduction
9.13.2 Chemical Reactions and Mass-Action Kinetics
9.13.3 Approximation by Separation of Timescales
9.13.4 Laplacian Dynamics and the Matrix-Tree Theorem
9.13.5 Chemical Reaction Network Theory
9.13.6 Algebraic Approaches
9.13.7 Conclusion
REFERENCES
Mathematical Modeling of Complex Biological Systems
9.14 From Genes and Molecules to Organs and Organisms: Heart
9.14.1 Introduction
9.14.2 The Cardiac Ventricular Action Potential
9.14.3 Propagation of the Cardiac Action Potential
9.14.4 The Electric Field of the Heart
Acknowledgments
REFERENCES
9.15 Biophysical Representation of Kidney Function
9.15.1 Kidney Structure and Function
9.15.2 Glomerular Function
9.15.3 Epithelial Function
9.15.4 Conclusion
Acknowledgment
REFERENCES
9.16 Systems Immunology: A Primer for Biophysicists
9.16.1 Introduction
9.16.2 Overview of Systems Immunology
9.16.3 Modeling T-Cell Activation Quantitatively
9.16.4 T-Cell Proliferation and Differentiation
9.16.5 Conclusion
REFERENCES
Index
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