Biological Kinetics

Biological Kinetics - Biological Kinetics K. Dane Wittrup...

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Biological Kinetics K. Dane Wittrup & Bruce Tidor October 10, 2007
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Contents 2 Noncovalent Binding Interactions 1 2.1 Specifc protein binding events are responsible For many biological Functions. . . . 1 2.2 Kinetic rate constants. ................................ 2 2.2.1 Typical ranges For k on and k oFF ........................ 4 2.3 Protein Binding InterFaces . ............................. 5 2.3.1 Statistical analyses oF protein–protein interFace amino acid composition . . 5 2.3.2 Alanine scanning. .............................. 5 2.4 Contributions to binding aFfnity . .......................... 7 2.4.1 Electrostatics. 7 2.4.2 Hydrogen bonding . 1 0 2.4.3 Van der Waals interactions. ......................... 1 1 2.4.4 Hydrophobic eFFect. 1 2 2.4.5 DeFormation energy and entropy. ...................... 1 4 2.4.6 Solvation . .................................. 1 5 2.5 Thermodynamics . 1 6 2.5.1 State Functions . ............................... 1 6 2.5.2 ±ree energy and standard states . 1 7 2.5.3 Thermodynamic cycle analysis. ....................... 2 6 Case Study 2-1 ”The use of double mutants to detect structural changes in the active site of the tyrosyl-tRNA synthetase (Bacillus stearothermophilus).”. P. J. Carter, G. Winter, A. J. Wilkinson, and A. R. Fersht. Cell 38 : 835–840 (1984). .................................... 3 0 Case Study 2-2 ”Do salt bridges stabilize proteins? A continuum electrostatic analysis.” Z. S. Hendsch and B. Tidor. Protein Sci. 3 : 211–226 (1994). .. 3 1
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ii CONTENTS
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Chapter 2 Noncovalent Binding Interactions “. . . teach us the nature of the ties which bind them together. ..” Socrates, quoted by Plato, in The Republic What causes one biomolecule to bind speciFcally to another? In this chapter we will examine the structures of protein complexes, their rates of formation, and the forces and energies that drive biological molecules to bind one another. The primary chemical forces include hydrogen bonding, electrostatics, van der Waals interactions, and the hydrophobic effect. Such binding interactions are generally noncovalent and reversible, and intermolecular contacts are visible in high-resolution, atomic-level structures of biomolecular complexes. Sometimes changes in structure and energetics within a partner also accompany binding, and intramolecular forces and energies are also important. This set of forces and energetics determine two fundamental characteristics of binding that we will return to throughout this book: the extent of binding (afFnity); and the rates of binding and unbinding (kinetics). Together these two properties generate much of the dynamics of biological systems. 2.1 Specifc protein binding events are responsible For many biologi- cal Functions. A signiFcant portion of biological function is mediated by protein–protein contacts, which are generally very speciFc. To get a feeling for the speciFcity of such interactions, consider that a cell’s cytoplasm is typically approximately 20–30% macromolecular solute by volume, which has been described as a condition of “macromolecular crowding” [14]. These solute molecules consist of thousands of different proteins, nucleic acids, and small organic metabolites. The images in ±igure 2.1 provide vivid graphic representations of the crowding encountered by proteins, both inside and outside of cells. This bears remembering as we draw highly simpliFed schematics
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2 CHAPTER 2. NONCOVALENT BINDING INTERACTIONS
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This note was uploaded on 07/19/2010 for the course BME 3604 taught by Professor Lt during the Spring '10 term at University of Florida.

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Biological Kinetics - Biological Kinetics K. Dane Wittrup...

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