welcome to chem 305! · chem 305 4) laying a foundations for new industries - developing databases...

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

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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

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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

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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)

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How can Biophysical Chemistry contribute?

Sample quality Structure Function

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Sample quality Structure Function

Is it pure? Does it contain species of different molecular weights?

Techniques to measure molecular size:• ultracentrifugation• electrophoresis• exclusion chromatography

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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

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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

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Sample quality Structure Function

What is the mechanism?

Thermodynamics and kinetics

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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

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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.

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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

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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?

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e.g. computer memory

R.R. Birge, Protein Based Computers, Scientific American, 90-95 (1995).

bacteriorhodopsin

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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

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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

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e.g. using new NMR techniques to gethigh resolution structures (1-2 Å)and automating the assignment andstructure calculation

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Develop new facilities!

Each node houses 1800 MHz NMR spectrometerand each arm houses a600MHz spectrometer!!

NMR:

http://www.gsc.riken.go.jp

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New synchrotron light sources for x-ray studies

http://www.psi.ch/sls

138 m

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Sample quality Structure Function

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Connection to Biophysical Chemistry (i.e. what we will learn this term)?

Structural genomics

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Sample quality Structure Function

Techniques to measure molecular weight:

• electrophoresis• analytical ultracentrifugation• light scattering

Techniques to measure concentration:

• absorbance

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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)