Chemical Relaxation in Molecular Biology

The development of an area of scientific research is a dynamic process with its own kinetic equations and its own physical mech­ anism. The study of fast chemical interactions and transformations is such an area, and while it is tempting to draw analogies or to speculate about the simplest model system, the lack of ade­ quately averaged observables is an annoying obstacle to such an undertaking. Sciences suffering from such conditions usually avoid quantitative models, be they primitive or complex. Instead, they prove their point by "case histories". Chemical relaxation kinetics started as an offspring of research in acoustics. In some aqueous ionic solutions anomalous acoustic absorption had been observed. A systematic study traced the cause of this absorption, showing that the covered frequency range and the intensity of the absorption were related in a predictable manner to the rate at which ions can interact and form structures differing in volume from the non interacting species. The step from this experimental observation and its correct, non­ trivial explanation to the discovery that all fast chemical pro­ cesses must reveal themselves quantitatively in the relaxation rate of a perturbed equilibrium state, and that perturbation para­ meters other than sound waves can be used for its exploitation, was made by MANFRED EIGEN in 1954. The foresightedness of K.F.

Theory and Simulation of Chemical Relaxation Spectra.- I. Introduction.- A. The Relaxation Kinetic Progress Curve.- B. Optical Detection Signals.- C. Theoretical Description of Relaxation Kinetics.- D. Single Reaction Steps.- E. Approximations for Complex Reaction Systems.- F. Average Relaxation Times.- G. Computer Program for Simulation of Relaxation Spectra (FORTRAN IV).- 1. Numbering of Reacting Species.- 2. Numbering of Individual Reaction Steps.- References.- Concentration Correlation Analysis and Chemical Kinetics.- I. Introduction.- II. Properties of Thermodynamic Fluctuations.- A. Magnitude of Occupation Number Fluctuations.- B. Dissipation of Number Fluctuations.- III. Measurement of Number Fluctuations.- A. Fluorescence Correlation Analysis (FCA).- 1. Design of the FCA Experiment.- 2. Correlation Computers.- 3. Experimental Results.- B. Resistance Correlation Analysis (RCA).- C. Absorbance Correlation Analysis (ACA).- D. Quasi-Elastic Light Scattering (QELS) and Turbidity Correlation Analysis (TCA).- E. Orientation Correlation Analysis (OCA).- IV. Summary and Conclusions.- References.- Dynamics of Substitution at Metal Ions.- I. Introduction.- II. Formation of 1:1 Complexes with Small Ligands.- III. Formation of 1:1 Complexes with Large Ligands.- IV. The Effect of Bound Ligands.- A. Non-Ring Systems.- 1. Outer-Sphere Complex Formation.- 2. Labilisation of Remaining Water Molecules.- 3. Steric and Electronic Interaction Between Ligands.- 4. Coordination Number Change at the Metal.- B. Ring Systems.- V. Summary.- References.- Dynamics of Proton Transfer in Solution.- I. Introduction.- II. Theoretical Background of Proton Transfer.- A. Proton Affinities.- B. Stability of Hydrogen Bonded Molecular Complexes..- C. Potential Curves for Proton Transfer.- D. Dynamics of Proton Transfer in the Vapor Phase.- E. Gas Phase Solvation.- F. Theoretical Concepts and Mechanisms of Proton Transfer in Solution.- III. Proton Transfer in Aqueous Solution.- A. Intermolecular Proton Transfer.- B. Intramolecular Proton Transfer.- IV. Proton Transfer in Non-Aqueous Solvents.- A. Protic, Non-Aqueous Solvents.- B. Aprotic Solvents.- V. Biochemical Model Studies.- A. Amino Acids.- B. Purines and Pyrimidines.- 1. Formation of Hydrogen Bonded Complexes.- 2. Proton Transfer Reactions on Purines, Pyrimidines and Some Related Heterocyclic Compounds..- C. Coenzymes and Other Model Compounds.- D. Macromolecules.- VI. Polypeptides and Proteins.- A. Oligopeptides.- B. High Molecular Weight Polypeptides and Proteins..- VII. Experimental Techniques.- VIII. Conclusion.- IX. Other Review Articles and Books on Proton Transfer..- References.- Elementary Steps of Base Recognition and Hdlix-Coil Transitions in Nucleic Acids.- I. Introduction.- II. Elementary Steps of Bases Stacking.- A. Stacking of Monomer Bases and Hydrophobic Interactions.- B. Conformation Change of Single-Stranded Polynucleotides.- III. Ion Condensation to Polynucleotides.- IV. Recognition of Monomer Bases on a Polymer Template..- V. Helix-Coil Transition of Oligo(A)•Oligo(U).- A. Equilibrium Parameters According to the Cooperative Reaction Model.- B. Relaxation Data and Their Interpretation According to an “All or None” Model.- C. Unzippering at Helix Ends.- D. Chain Sliding.- VI. The Influence of GC Base Pairs.- VII. Specific Effects in Helix Loops.- VIII. Dynamics of Polymer Helix-Coil Transitions.- IX. Rate and Specificity of Genetic Information Transfer.- X. Summary.- References.- Structural Dynamics of tRNA. A Fluorescence Relaxation Study of tRNA.- I. Introduction.- II. Fluorescent Probes for the Structure of tRNA.- III. Pulsed Fluorescence Measurements.- A. The Lifetime of Excited States of the Fluorescent Probe and the Distribution of Conformational States.- B. Rotational Brownian Motion and Time-Dependent Fluorescence Anisotropy.- C. Instrumentation.- D. Results.- IV. Measurements Under Stationary Excitation.- V. Measurements of Chemical Rates.- A. Instrumentation and Data Evaluation.- B. Results.- VI. A Model for Aliosteric Conformations of tRNA.- A. Evaluation of the Parameters.- VII. Conformational States of tRNA with Regard to the Biological Role of tRNA.- References.- Chemical Relaxation Kinetic Studies of E. eoli RNA Polymerase Binding to Poly[d(A-T)] Using Ethidium Bromide as a Fluorescence Probe.- I. Introduction.- II. Experimental Procedures and Data Analysis.- A. Materials.- B. Fluorescence Temperature-Jump Measurements. Instrumentation and Conditions.- C. On-Line Computer Acquisition of Relaxation Data..- D. Analysis of Relaxation Curves by the Method of Modulating Functions.- III. Excluded Site Binding of Ethidium Bromide to Poly [d (A-T)].- A. Theory for the Equilibrium State.- B. Theory for Relaxation Kinetic Behavior.- C. Experimental Results and Analysis.- IV. Relaxation Kinetics of Ethidium Bromide and Poly [_d (A-T) J in the Presence of RNA Polymerase.- A. Experimental Conditions.- B. Experimental Results, Analysis, and Model Fitting.- V. Conclusions.- VI. Appendix. On the Derivation of General Equations for Relaxation Kinetics of Systems with Excluded Binding.- References.- Protein Folding and Unfolding.- I. Introduction.- II. Time-Independent Phenomena.- A. Van’t Hoff Analysis of Unfolding Reactions.- B. Recent Calorimetric Results.- III. “Slow” Temperature-Jump Methods.- A. Cells for Optical Measurements.- B. Cell for pH-Measurements.- C. Switching Unit and Thermostates.- D. Other Methods of Temperature Perturbation.- IV. Kinetics of Unfolding and Refolding.- A. Kinetic Difference Spectra.- B. Steady State Rates.- C. Transient Kinetics.- V. Theoretical Approach to the Kinetics of Folding.- A. Simple Sequential Model.- B. Lattice Model.- C. Isomerization Model.- D. Outline of a Phénoménologie Description.- E. Computer Simulation.- F. Outlook.- References.- Kinetics of Antibody-Hapten Interactions.- I. Introduction.- II. The Kinetics of the Association Step.- Concluding Remarks.- III. Kinetic Expression of the Elementary Interactions.- IV. Conformational Transitions Induced by Hapten Binding.- References.- Glutamate Dehydrogenase Self-Assembly. An Application of the Light Scattering Temperature-Jump Technique to the Study of Protein Aggregation.- I. Introduction.- II. Structural Features.- III. Thermodynamics of Self-Assembly.- A. Models.- B. Nonideality.- C. Nature of Interactions Between Oligomers.- D. Polymer Distribution.- IV. Scattered Light Detection in Chemical Relaxation Experiments.- A. Angular Dependence.- B. The Role of Virial Coefficients.- V. Kinetics of Self-Assembly.- A. The Sequential Model.- B. The Random Association Model.- C. Treatment of Kinetic Results.- D. Summary of Kinetic Results.- References.- Dynamic Aspects of Carrier-Mediated Cation Transport Through Membranes.- I. Introduction and General Considerations.- A. Biological Relevance.- B. Model Systems: Cation Selectivity of Antibiotics..- II. Kinetic Studies on Lipid Bilayer Membranes.- III. Elementary Steps Involved in Carrier-Mediated Cation Transport.- A. Elementary Steps Relevant to Proton Transport.- 1. Thermodynamic Parameters.- 2. Kinetics of Proton Transfer.- B. Elementary Steps Relevant to Alkali Ion Transport.- 1. Conformational Properties and Localization of Alkali Ion Specific Antibiotics in Membranes..- 2. Thermodynamic Aspects of Alkali Ion Specificity and Structure of Cation Complexes.- 3. The Kinetics and Mechanism of Complex Formation with Alkali Ions and Its Relevance to Cation Specificity.- IV. Comparison of the Dynamic Aspects of Cation Carriers Bound to Membranes and in Homogeneous Solution.- V. Summary.- References.