Post on 28-Jan-2020
CHEM 305
Welcome toCHEM 305!
CHEM 305
Suzana Straus
Office: D405Office hours: Wed: 12:00-1:30
email: sstraus@chem.ubc.ca
Research interests: - Biophysical Chemistry- Membrane Proteins- Solid state nuclear magnetic resonance (NMR)
CHEM 305
Course OutlineWeek of Jan. 5: Introduction; Math review/Distributions
Week of Jan. 10: Diffusion in one, two, and three dimensionsRandom walk
Week of Jan. 17: Diffusion in one, two, and three dimensionsFick’s Laws
Week of Jan. 24: Electrophoresis; Review for midtermMIDTERM 1: Friday Jan. 28th, 11-12
Week of Jan. 31: Sedimentation; Svedberg equationShape factors
Week of Feb. 7: Equilibrium sedimentation
Week of Feb. 14: Midterm break
Week of Feb. 21: Viscosity
CHEM 305
Course Outline (continued)Week of Feb. 28: Classical description of periodic phenomena;
Electromagnetic wavesMIDTERM 2: Friday Mar. 4th, 11-12
Week of Mar. 7: Scattering; Zimm plots; Beer-Lambert law
Week of Mar. 14: Circular dichroim; Optical rotary dispersion
Week of Mar. 21: Absorbance; Nuclear magnetic resonance
Week of Mar. 28: Nuclear magnetic resonance; X-rayCrystallography
Week of Apr. 4: Review for final (last day of term, April 8th)
CHEM 305
Grading scheme
50% Final25% Best mark from either Midterm 1 or Midterm 225% 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 behanded out and discussed on the following Wednesday. You are stronglyencouraged to try to complete the assignments!
CHEM 305
Course notes and supplementary material
All notes are posted at: http://www.chem.ubc.ca/courseware/305/Chem305.htmlor are available for purchase.
Books:
1) Title: Techniques for the study of biological structure and functionAuthor: Cantor, Charles R., 1942-
Schimmel, Paul Reinhard, 1940-
Call number: QH345.C36 V. 2 (on reserve in Woodward Library)
Chapters 10-12
2) Title: Physical biochemistryAuthor: Van Holde, K. E. (Kensal Edward), 1928-
Call number: QT34.V35 1971
Chapters on absorption, circular dichroism, x-ray crystallography
CHEM 305
Structural Genomics
Proteomics
CHEM 305CHEM 305
Structural genomics and proteomics
In the last few years, scientists have successfully identified the genomesof a number of organisms and animals, including humans (Human GenomeProject – for more information see http://www.ornl.gov/TechResources/Human_Genome/home.html)
CHEM 305CHEM 305
How can Biophysical Chemistry contribute?
Sample quality Structure Function
CHEM 305CHEM 305
Sample quality Structure Function
Is it pure? Does it contain species of different molecular weights?
Techniques to measure molecular size:• ultracentrifugation• electrophoresis• exclusion chromatography
CHEM 305CHEM 305
Sample quality Structure Function
Is it native? Is it complete?Is it consistent?
In vivo studies – difficultIn vitro studies – if possible, check that the activity is preserved
using assays
CHEM 305CHEM 305
Sample quality Structure Function
What is the structure?
Primary structure – sequencingSecondary structure – optical spectroscopy (e.g. CD), NMRTertiary structure – NMR, x-ray crystallography, diffraction techniques,
techniques to measure distanceSize and shape – electron microscopy, hydrodynamic techniques
CHEM 305CHEM 305
Sample quality Structure Function
What is the mechanism?
Thermodynamics and kinetics
CHEM 305CHEM 305
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 methodsthat 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: http://www.gsc.riken.go.jp/e/gsc/futureE.html
CHEM 305
e.g. Rice genome
- Knowing the genetic sequences allowsbiotech companies to create “blast free”rice
- Blast is a fungal disease which affectsproduction – losses on the order of 55million US dollars per year.
CHEM 305CHEM 305
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
CHEM 305
e.g. developing new HIV drugs
- Knowing the structure of HIV proteaseand understanding drug entry and releasewill lead to a new generation of inhibitors
CHEM 305CHEM 305
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 willenable us to understand and manipulate these biomolecules so that newdrugs can be developed to cure different diseases, new materials can be developed,etc.
How do we achieve the aim of structural genomics?
CHEM 305
e.g. computer memory
R.R. Birge, Protein Based Computers, Scientific American, 90-95 (1995).
bacteriorhodopsin
CHEM 305CHEM 305
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!!!!)
http://www.rcsb.org/pdb/holdings.html
CHEM 305CHEM 305
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 powerfulcomputerclusters
CHEM 305CHEM 305
e.g. using new NMR techniques to gethigh resolution structures (1-2 Å)and automating the assignment andstructure calculation
CHEM 305CHEM 305
Develop new facilities!
Each node houses 1800 MHz NMR spectrometerand each arm houses a600MHz spectrometer!!
NMR:
http://www.gsc.riken.go.jp
CHEM 305CHEM 305
New synchrotron light sources for x-ray studies
http://www.psi.ch/sls
138 m
CHEM 305CHEM 305
Sample quality Structure Function
?
Connection to Biophysical Chemistry (i.e. what we will learn this term)?
Structural genomics
CHEM 305CHEM 305
Sample quality Structure Function
Techniques to measure molecular weight:
• electrophoresis• analytical ultracentrifugation• light scattering
Techniques to measure concentration:
• absorbance
CHEM 305CHEM 305
Sample quality Structure Function
Secondary structure – optical spectroscopy (e.g. CD, ORD), NMRTertiary structure – NMR, x-ray crystallographySize and shape – hydrodynamic techniques (e.g. viscosity, diffusion,
friction); radius of gyration (light scattering)