Contents -- Preface -- About the Authors -- Chapter 1 Molecular Behavior in Biological Cells: The Bacterial Cytoplasm as a Model System Adrian H. Elcock and Andrew S. Thomas -- 1. Introduction -- 2. A Simple Analogy for Molecular Behavior in vivo -- 3. Macromolecular Crowding Effects -- 4. The Bacterial Cytoplasm as a Model System -- 5. A Structural Model of the Bacterial Cytoplasm -- 6. Some Issues in Simulating Such a System -- 7. A Dynamic Model of the Bacterial Cytoplasm -- 8. Quantifying Protein Diffusion in the Bacterial Cytoplasm -- 9. Thermodynamic Stability of Proteins in the Bacterial Cytoplasm -- 10. Conclusion -- Acknowledgments -- Suggested Additional Reading Material -- References -- Chapter 2 The Light-Harvesting Apparatus in Purple Photosynthetic Bacteria: Introduction to a Quantum Biological Device Johan Strümpfer, Jen Hsin, Melih Şener, Danielle Chandler and Klaus Schulten -- 1. Introduction -- 2. Components of a Chromatophore Vesicle -- 2.1 The light-harvesting complex LH2 -- 2.2 The RC-LH1 core complex -- 2.2.1 Organization of RC-LH1 -- 2.2.2 Structures of LH1 and RC -- 2.3 Spatial organization of the chromatophore -- 3. Energy Harvesting and Transfer -- 3.1 Excitons -- 3.2 Excitation transfer -- 3.3 Chromatophore-wide exciton transfer -- 4. Discussion -- Acknowledgments -- References -- Appendix -- Chapter 3 DNA Polymerases: Structure, Function, and Modeling Tamar Schlick -- 1. Introduction -- 1.1 Venerable task -- 1.2 Replication and repair fidelity -- 1.3 Polymerase structure and function -- 2. Modeling Studies -- 2.1 Need for modeling -- 2.2 Conformational pathways in pol β, pol λ, pol X, and pol µ -- 2.3 Pol β's closing pathway -- 2.4 Pol β's chemical mechanism for G:C vs. G:A systems -- 2.5 Pol λ's pathway and slippage tendency -- 2.6 Dpo4's handling of 8-oxoG -- 2.7 Pol X mispair incorporation -- 3. Conclusion.

Acknowledgment -- Suggested Additional Reading Materials -- References -- Chapter 4 Information Processing by Nanomachines: Decoding by the Ribosome Karissa Y. Sanbonmatsu, Scott C. Blanchard and Paul C. Whitford -- 1. Introduction -- 2. Overview of Protein Synthesis and Elongation -- 3. Decoding by the Ribosome -- 4. Dynamic Regions of the Ribosomal Complex -- 4.1 Dynamic regions of the ribosome -- 4.2 tRNA as an active player in decoding: Flexible tRNAs -- 5. Computational Studies of Decoding by the Ribosome -- 5.1 Early simulations of decoding and tRNA selection -- 5.2 REMD simulations of the decoding center produce exhaustive sampling -- 5.3 High performance computing systems are required to simulate the intact ribosome -- 5.4 Simulations of large-scale conformational changes of tRNAs -- 6. Towards Energy Landscapes of Decoding -- Suggested Additional Reading Materials -- References -- Chapter 5 Chaperonins: The Machines Which Fold Proteins Del Lucent, Martin C Stumpe and Vijay S Pande -- 1. Introduction -- 2. GroEL -- 3. How Do Chaperonins Work? -- 3.1. The Anfinsen cage hypothesis -- 3.2. Iterative annealing -- 3.3. The landscape modulation hypothesis: Confinement -- 3.4. The landscape modulation hypothesis: Chaperonin-enhanced hydrophobic effect -- 4. Other Chaperonins -- 5. Conclusions -- Suggested Additional Reading Materials -- References -- Chapter 6 Muscle and Myosin Ronald S. Rock -- 1. A Structural Basis for Motion -- 2. Coupling of Motion to ATP Hydrolysis -- 3. In Vitro Motility Assays Reconstitute Motion from a Minimal Set of Components -- 4. The Stepsize Controversy and Single Molecule Motility -- 5. From Swinging Crossbridges to Sliding Filaments -- 6. The Regulation of Contraction -- 7. New Frontiers in Motility Research: Nonmuscle Myosins and the Evolution of Eukaryotic Motility -- Suggested Additional Reading Material.

References -- Chapter 7 Protein Kinases: Phosphorylation Machines Elaine E. Thompson, Susan S. Taylor and J. Andrew McCammon -- 1. Introduction -- 2. Activation Loop -- 3. DFG Loop -- 4. C-helix -- 5. Kinase Spines -- 6. Processive Phosphorylation -- 7. Conclusion -- Acknowledgments -- Suggested Additional Reading Materials -- References -- Chapter 8 Computational Studies of Na /H Antiporter: Structure, Dynamics and Function Assaf Ganoth, Raphael Alhadeff and Isaiah T. Arkin -- 1. Introduction -- 2. Structure of the Na /H Antiporter -- 3. The Dynamics of the Na /H Antiporter -- 3.1 The influence of protonation states on the NhaA -- 3.2 Mechanism of Na /H antiporting -- 3.3 The unique Na /H electrostatic organization -- 4. Models for the Na /H Proteins -- 4.1 Model structure of the vibrio parahaemolyticus NhaA -- 4.2 Model structure of NHE1 - A human Na /H exchanger -- 4.3 Model structure of NHA2 - A human Na /H antiporter -- 5. Concluding Remarks -- Acknowledgments -- Suggested Additional Reading Materials -- References -- Chapter 9 Membrane Transporters: Molecular Machines Coupling Cellular Energy to Vectorial Transport Across the Membrane Zhijian Huang, Saher A. Shaikh, Po-Chao Wen, Giray Enkavi, Jing Li and Emad Tajkhorshid -- 1. Introduction -- 2. ATP-Driven Transport in ABC Transporters -- 3. Ion-Coupled Neurotransmitter Uptake by the Glutamate Transporter -- 4. Substrate-Induced Rocker-Switch Motion in an Antiporter -- 5. Alternating Access Model in Leucine Transporter -- 6. Interconversion of the Open and Occluded States in Na -Coupled Galactose Transporter -- 7. Concluding Remarks -- Acknowledgment -- Suggested Additional Reading Materials -- References -- Chapter 10 ABC Transporters E. P. Coll and D. P. Tieleman -- 1. Introduction -- 2. Structure of ABC Transporters -- 2.1 NBD structure -- 2.2 TMD structure -- 2.2.1 Importers.

2.2.2 Type I importers -- 2.2.3 Type II importers -- 2.2.4 Exporters -- 3. Transport Cycle -- 4. Methods of Study -- 5. Conclusions -- Acknowledgments -- References -- Chapter 11 Sodium-coupled Secondary Transporters: Insights from Structure-based Computations Elia Zomot, Ahmet Bakan, Indira H. Shrivastava, Jason DeChancie, Timothy R. Lezon and Ivet Bahar -- 1. Introduction: Biological Function and Classification -- 2. Na -Coupled Mechanism of Transport: A Macroscopic View -- 2.1 Transport cycle and alternate access mechanism -- 2.2. Balance of forces/potentials across the membrane favors Na inward flow -- 2.3 Sodium ion co-transport as a driving potential for the transmembrane translocation of solutes by secondary transporters -- 3. Structural Information -- 3.1 Structure and topology -- 3.2 Substrate and sodium binding -- 4. Molecular Mechanisms Revealed by Structure-Based Modeling and Computations -- 4.1 Local Motions and Substrate/Sodium Interactions in Glutamate Transporters -- 4.1.1 Gate opening in the outward-facing state of Glt -- 4.1.2 Role of Na ions in stabilizing the closed conformation of the EC gate in the substrate-bound outward-facing Glt -- 4.1.3 Na and substrate release by Glt in the inward-facing state -- 4.2 Conformational dynamics of NSS family members and their structural homologs -- 4.2.1 Molecular dynamics of transporters that share the LeuT fold -- 4.2.2 Spontaneous release of Na and dislodging of substrate observed in MD simulations of galactose transporter vSGLT -- 5. Transitions between Inward- and Outward-Facing States Explored by Computational Analyses -- 5.1 Structure prediction via homology modeling based on structural symmetry -- 5.1.1 Modeling of Glt in the inward-facing state based on the outward-facing structure -- 5.1.2 Modeling of LeuT in the inward-facing state based on known outward-facing structure.

5.2 Results from elastic network models -- 6. Conclusion -- References -- Chapter 12 Voltage-Gated Ion Channels: The Machines Responsible for the Nerve Impulse Benoît Roux and Francisco Bezanilla -- 1. Introduction -- 2. Biological Membranes and Channels -- 3. The Nernst Potential -- 4. Selective Channels and the Action Potential -- 5. Channel Function at the Atomic Level -- 5.1 Fast ion conduction and selectivity -- 5.2 Channel gating and membrane voltage -- 5.3 The functional implications of a focused field -- 6. Future Outlook -- Suggested Additional Reading Materials -- References -- Chapter 13 Voltage-Gated Channels and the Heart Jonathan R. Silva and Yoram Rudy -- 1. Introduction -- 2. Cardiac Electrophysiology Background -- 2.1 Organ level physiology -- 2.2 Cellular level electrophysiology -- 2.2.1 The Hodgkin-Huxley model -- 2.2.2 Modeling the cardiac ventricular action potential -- 2.2.3 Rate dependence -- 2.2.4 β-adrenergic regulation -- 2.2.5 The long QT syndrome -- 3. I as a Molecular Machine -- 3.1 Structure and kinetics -- 3.2 Kinetic modeling of I -- 3.3 Molecular modeling of I -- Conclusion -- Further Reading -- References -- Index.