Introduction; Math review/distributions. Diffusion in one, two, and three dimensions Random walk. Fick s Laws

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1 Welcome to!

2 Suzana Straus Office: Office hours: D405 Wed: 12:00-1:30 Research interests: - Biophysical Chemistry - Membrane Proteins - Solid state nuclear magnetic resonance (NMR)

3 Course Outline Week of Jan. 5: Week of Jan. 10: Week of Jan. 17: Week of Jan. 24: Week of Jan. 31: Week of Feb. 7: Week of Feb. 14: Week of Feb. 21: Introduction; Math review/distributions Diffusion in one, two, and three dimensions Random walk Diffusion in one, two, and three dimensions Fick s Laws Electrophoresis; Review for midterm MIDTERM 1: Friday Jan. 28 th, Sedimentation; Svedberg equation Shape factors Equilibrium sedimentation Midterm break Viscosity

4 Course Outline (continued) Week of Feb. 28: Week of Mar. 7: Week of Mar. 14: Week of Mar. 21: Week of Mar. 28: Classical description of periodic phenomena; Electromagnetic waves MIDTERM 2: Friday Mar. 4 th, Scattering; Zimm plots; Beer-Lambert law Circular dichroim; Optical rotary dispersion Absorbance; Nuclear magnetic resonance Nuclear magnetic resonance; X-ray Crystallography Week of Apr. 4: Review for final (last day of term, April 8 th )

5 Grading scheme 50% Final 25% Best mark from either Midterm 1 or Midterm 2 25% Lab and reports for five experiments: - Optical rotatory dispersion - Sedimentation coefficient of bovine serine albumin - Determination of molecular weight by viscosity - Light scattering - Diffusion 100% Weekly assignments will be handed out every Wednesday. Solutions will be handed out and discussed on the following Wednesday. You are strongly encouraged to try to complete the assignments!

6 Course notes and supplementary material All notes are posted at: or are available for purchase. Books: 1) Title: Techniques for the study of biological structure and function Author: Cantor, Charles R., Schimmel, Paul Reinhard, Call number: QH345.C36 V. 2 (on reserve in Woodward Library) Chapters ) Title: Physical biochemistry Author: Van Holde, K. E. (Kensal Edward), Call number: QT34.V Chapters on absorption, circular dichroism, x-ray crystallography

7 Structural Genomics Proteomics

8 Structural genomics and proteomics In the last few years, scientists have successfully identified the genomes of a number of organisms and animals, including humans (Human Genome Project for more information see Human_Genome/home.html)

9 How can Biophysical Chemistry contribute? Sample quality Structure Function

10 Sample quality Structure Function Is it pure? Does it contain species of different molecular weights? Techniques to measure molecular size: ultracentrifugation electrophoresis exclusion chromatography

11 Sample quality Structure Function Is it native? Is it complete? Is it consistent? In vivo studies difficult In vitro studies if possible, check that the activity is preserved using assays

12 Sample quality Structure Function What is the structure? Primary structure sequencing Secondary structure optical spectroscopy (e.g. CD), NMR Tertiary structure NMR, x-ray crystallography, diffraction techniques, techniques to measure distance Size and shape electron microscopy, hydrodynamic techniques

13 Sample quality Structure Function What is the mechanism? Thermodynamics and kinetics

14 Goal of the structural genomics: - solve 10,000-20,000 protein structures Why bother? 1) Continuous production and procurement of food - Improvement of grain production - Establishment of environmentally sound practices methods that do not require the use of pesticides - Creating lands suitable for farming out of extreme environments - Establishment of diagnostic methods for genetic diseases for livestock - Development of radically new breeds and preservation of the environment - Development of disease-resistant crops - Development of crops able to withstand extreme environments - Radical changes in agricultural technologies - Development of super high-yield and labor-saving crops taken from:

15 e.g. Rice genome - Knowing the genetic sequences allows biotech companies to create blast free rice - Blast is a fungal disease which affects production losses on the order of 55 million US dollars per year.

16 2) Preservation of the environment - Decomposition and elimination of raw oil and gasoline - Improvement of contaminated underground water and recovery of high-nutrition ponds and lakes - Greening of desert regions - Reducing loads on the earth's environment through the use of completely biodegradable materials - Development of environmentally friendly materials - Improvement of contaminated underground water and recovery of high-nutrition ponds and lakes - Greening of desert regions - Reducing loads on the earth's environment through the use of completely biodegradable materials 3) Application to medicine - Conquering cancer, diabetes, hypertension and allergy - Preventing diseases by high-speed and accurate diagnoses - Developing bone marrow transplantation techniques using blood stem cells - Improving technology for the manufacture of artificial skin & blood - Developing and making gene therapy widely available - Development of new drugs - Creation of biologically suitable materials that don t induce rejection - Development of new therapies

17 e.g. developing new HIV drugs - Knowing the structure of HIV protease and understanding drug entry and release will lead to a new generation of inhibitors

18 4) Laying a foundations for new industries - Developing databases for human gene information - Developing equipment systems utilizing biological functions: such as biosensor, biochip, micromachines, etc - Application to the chemical industry and energy production: such as bioreactor, biomass, etc - Development of genetic information databases - Development of bioequipment - Development of high-function bioprocessors In other words, knowledge of the three-dimensional structure of all proteins will enable us to understand and manipulate these biomolecules so that new drugs can be developed to cure different diseases, new materials can be developed, etc. How do we achieve the aim of structural genomics?

19 e.g. computer memory bacteriorhodopsin R.R. Birge, Protein Based Computers, Scientific American, (1995).

20 Start off by not solving all structures!!! - organize the proteins into families - select representative members (ca. 10,000 structures over the next 10 years) - solve the 3D structure using x-ray crystallography and NMR - build models for homologues (millions of structures!!!!)

21 We also need to speed up the process of obtaining three-dimensional structures. 1) by developing improved methodology: E.g. Structure determination in 4.5 hours using powerful computer clusters

22 e.g. using new NMR techniques to get high resolution structures (1-2 Å) and automating the assignment and structure calculation

23 Develop new facilities! NMR: Each node houses MHz NMR spectrometer and each arm houses a 600MHz spectrometer!!

24 New synchrotron light sources for x-ray studies 138 m

25 Connection to Biophysical Chemistry (i.e. what we will learn this term)? Structural genomics Sample quality Structure Function?

26 Sample quality Structure Function Techniques to measure molecular weight: electrophoresis analytical ultracentrifugation light scattering Techniques to measure concentration: absorbance

27 Sample quality Structure Function Secondary structure Tertiary structure Size and shape optical spectroscopy (e.g. CD, ORD), NMR NMR, x-ray crystallography hydrodynamic techniques (e.g. viscosity, diffusion, friction); radius of gyration (light scattering)