1st Class
- Tues.
8/28/07
Overview of course, We started by going
over the
course syllabus at (http://www.udel.edu/chem/bahnson/Chem641).
Next, Biochemistry was introduced with a brief
introduction
to macromolecules, how they are made, and the forces that hold them
together.
We watched a brief movie that can be viewed from the NIH web
site:
(http://www.nhgri.nih.gov/educationkit/).
It gave an overall view of where proteins are made from the information
in your genome. We looked at a table of the genetic code at a
link here,
and we introduced some chime demos that we will be using to appreciate
macromolecular structures (click
here).
Finally, we got started with the course. I
introduced
the weak forces: van der Waals, hydrogen bonds, ionic interactions, and
hydrophobic effects.
Assignment: read Chapters 1 and 2 of text
Lehninger, 4th
edition. problem
set #1 was assigned.
2nd Class
- Thurs.
8/30/07
pH, Water and Ionic Equilibria
- Coming
from the introduction of the first class, we discussed the properties
of
water. These were contrasted to how a biological lipid bilayer
(membrane)
is made. Then we came back to the weak force: "the
hydrophobic
effect". Here, we introduced the concept of order/disorder and
entropy
to help explain the hydrophobic effect. Then we reviewed various
basics, such as how to calculate the pH of a weak acid. We then
derived
the Henderson-Hasselbalch equation and showed how it is used to
calculate
pHs of buffer systems. Finally we went over the ionic-equilibria
of a polyprotic acid.
Assignment: read Chapter 3 of Lehninger.
3rd Class
- Tues.
9/4/07
Amino Acids - Reviewed D,L and R,S
conventions
for assigning chirality, acid-base properties of amino acids, and then
went over the 20 commonly occurring L-amino acids. Several
concepts
were introduced from the various side chains of the amino acids
including:
isoelectric point, zwitterionic, general acid/base catalysis, cysteine
disulfide bonds.
I sent the class home with an extra
assignment:
to design an enzyme active site, using the side chains of His and Asp
to
perform general acid/base catalysis on the first step of an esterolysis
reaction.
Assignment: Continue reading Chapter 3 of text Lehninger, 4th edition. problem set #2 was assigned. Posted today: Problem set #1 answers.
4th Class
- Thurs.
9/6/07
Peptide Bonds - Discussed peptide bonds,
introduced
peptide planes, Phi and Psi tortion angles, cis vs. trans peptide
bonds,
and allowed conformations. We then shifted to computer
visualization
with kinemage graphics that are from a supplement to the textbook
by Branden & Tooze titled "Introduction to Protein Structure" 2nd.
Edition. Click
here for a complete local copy of the kinemage files
available.
In class we talked about a couple of views from the kinemage file C1BASICS.KIN.
In order to view this file, right click and save as, on your
computer.
Then you need to open this file with the MAGE_5_4.EXE
executable file. You can go to the official kinemage home page by
clicking
here. If you are a mac user you can get a copy of the
software
from that page.
Finaly, we discussed protein sequence alignments
and
visited a couple of web sites that are usefull for the protein
alignment
problem in problem set #2.
To get a protein sequence - http://www.ncbi.nlm.nih.gov/entrez/
and select protein on top left of page.
To align sequences - http://www.ncbi.nlm.nih.gov/BLAST/
and select Blast 2 sequences.
Assignment: Begin reading Chapter 4 of text Lehninger, 4th edition.
5th Class
- Tues.
9/11/07
Secondary Structure - What are allowed Phi
and
Psi angles, The Ramachandran Plot, Alpha-helices, Beta-sheets parallel
and anti-parallel, beta-turns. We will discuss protein folding as
well. I handed out supplementary notes that show secondary
structure
in 2-dimensions (click
here to get another copy). We looked at
secondary
structures from several graphics programs:
the chime
demo pages - links to alpha helices and beta sheets
We also saw a molecular dynamics movie of a
peptide folding
from Yong Duan's group at UC Davis (formerly from UD). You can
download
the two version of the movie:
stick
figure version - 70 MB is size.
space
filling version - 30 MB size
Assignment: Continue reading Chapter 4 of text Lehninger, 4th edition. problem set #3 was assigned. Posted today: Problem set #2 answers.
6th Class
- Thurs. 9/13/07
Tertiary and Quaternary Protein Structure
- Overview
of levels of protein structure: primary, secondary, tertiary,
quaternary.
You can download a brief powerpoint used at beginning of class here
and the Hb dynamics movie here.
For a pdf version click here.
Described 4 classes of globular proteins: anti-parallel alpha helix,
parallel
beta-sheets, antiparallel beta-sheets, and metal/disulfide rich
proteins.
Showed examples of these protein fold classes
from the
Kinemages from Branden and Tooze, remember to right click to save files
below to computer and use the Kinemage
software to open the files:
C2MOTIFS.KIN
- an overview of super secondary structure
C3ALPHA.KIN
- anti-parallel alpha helix motif
C4AL_BET.KIN
- beta-alpha-beta motif
C5BETA.KIN
- antiparallel beta sheet proteins
Go to the SCOP database to see how
protein folds are classified into subsets. http://scop.berkeley.edu/
Assignment: pgs.89-96, section 3.3 of text
Lehninger,
4th edition.
Also read pgs 489-495, reviewing Thermodynamics for PS #3.
7th
Class - Tues.
9/18/07
Protein Techniques
Protein over expression, purification and
analysis techniques
were covered. We also discussed the heterogeneity/homogeneity of
proteins.
You can get a pdf version of the class powerpoint
file here.
Assignment: pgs. 136-139 of text Lehninger,
4th edition.
Also click here to print out slides for our next
class ahead of time.
problem
set #4 was assigned. Posted today: Problem
set #3 answers.
8th Class
- Thurs.
9/20/07
Protein Structure Determination: X-ray
Crystallography,
NMR Spectroscopy and Homology Modeling
Other Usefull Links :
Nature
of 3-D Structural Data - Link from the Protein Data Bank that
gives a short overview and links to books to read up on techniques
PDF
file from the book Protein Structure and Function, Petsko and
Ringe,
New Sciences Press LTD, 2004.
Crystallography
101 - an informative web site
PDF
version of the slides from our class (2 slides per page).
PDF
version of the slides from our class (6 slides per page).
Assignment: pgs. 157-174, section 5.1 of Lehninger, 4th edition.
9th
Class
- Tues.
9/25/07
Hemoglobin and Cooperativity
We recapped crystallography, homology modeling and NMR methods to
obtain structural models. Then we discussed ligand bind,
cooperativity and ties to structure using Hb and Mb as a model
system. Some powerpoint slides can be printed out as a pdf by clicking here.
Hb dynamics movie here.
Assignment: continue
reading Chapter 5, section 5.2, pgs. 174-182 of
Lehninger,
4th edition. problem
set #5 was assigned. Posted today: Problem
set #4 answers.
10th
Class
- Thurs.
9/27/07
Complementary Interactions
between Proteins and Ligands
Today, we finished up hemoglobin cooperativity by discussing the
stabilizing of R vs. T state to fine tune its function. Then we
quickly looked at the cause of Sickle Cell Anemia. Demos were
shown that you can access from the Lehninger website.
We discussed antibodies using a demo of
Fab-lysozome (click
here). Here we introduced terms such as polyclonal,
monoclonal, antigen, epitope Affinity chromatography, ELISA, and
westerns were discussed with an example of phosphorylated proteins.
Then we talked about catalytic
antibodies. You could read ahead about this on page 221 of
Lehninger. Finally this was tied into the principle of an enzyme
binding its transition sate, as well as stategies of inhibiting an
enzyme with high binding affinity.
We ended with a brief demo of HIV protease binding the drug Ritonavir (click here).
Assignment: read pgs. 190-208 Chapter 6 of
Lehninger,
4th edition.
11th
Class
- Tues.
10/2/07
Enzyme Kinetics
We continued our discussion of an enzyme binding the
transition-state. Then presented simple kinetic schemes and
reaction coordinate diagrams for an enzyme reaction. First order
and second order kinetics were reviewed. Then we discussed the
steady state approximation and Michaelis-Menton Enzyme Kinetics.
We finished by discussing general approaches that enzymes use to
catalyze reactions beyond binding the transition-state.
A pdf with notes handed out in class can be downloaded here.
A study sheet for the upcoming exam can be downloaded here.
Assignment: read pgs. 213-225, section
6.4 - Examples of Enzymatic Reactions
of Lehninger.
No new problem set since we have an exam this Saturday.
Posted today: Problem
set #5 answers.
12th
Class
- Thurs.
10/4/07
Enzyme Mechanism
We applied what we know about weak force interactions, side chains, pH
equilibria, protein structure, ligand binding and enzyme kinetics to
the alcohol dehydrogenase catalyzed reaction. Click
here to get a pdf file of today's powerpoint.
Two Review Sessions
-
Thurs 10/4 and Fri 10/5, 7:30-9pm, both evenings in Gore 205. Come prepared with questions.
First Exam -
Saturday 10/6/05, 10a - noon, location: 100 KRB
Answers for Exam 1 - click here
Distribution of Exam 1 - click here
Assignment: read section 13.2 (pgs. 496-507)
and 6.5 (pgs. 225-233) of
Lehninger,
4th edition.
13th Class
- Tues.
10/9/07 - Phosphoryl
Transfer Energetics and Introduction to Glycogen Phosphorylase - exams were handed back.
Gibbs free energy, Enthalpy and finally
Entropy. Then we
went through some more practical problems using delta-G to
determine
if a reaction will proceed in the forward direction, introduced
standard
state, non standard state corrections, interrelating delta-G and
Keq.
Then went to an example of PEP and ADP reacting to form pyruvate and
ATP.
Thermodynamic vs. kinetic control of a reaction. Physiological
example
of substrates and products of pyruvate kinase to calculate delta-G that
is not standard state. Then we introduced glycogen phosphorylase and
where
ATP and NAD+/NADH fit into metabolism, with a focus on
glycolysis.
Assignment:
Read sections 6.5 (pgs. 225-233) and 12.4 (pgs
435-445) Lehninger,
4th edition. problem
set #6 was assigned.
14th
Class - Thurs.
10/11/07 - Glycogen
Phosphorylase and the Epinephrine Cascade - Today the focus was on the allosteric / cooperative
properties
of glycogen phosphorylase (Sect. 6.5 Lehninger). Then we discussed
several ways enzyme are regulated, using the epinephrine cascade as an
example (Sect. 12.4 of Lehninger).
In the discussion we viewed several demos and
links:
(http://www.udel.edu/chem/bahnson/Chem641/chime/Index.htm)
We also looked at a couple of pdb
files of GP in its R-state and T-state (1gpa.pdb
and 3gpb.pdb)
using the program Deepview,
which
you can download for free.
Here is a class handout in pdf format
Assignment: re-read Chapter 6, section 6.4, pgs. 213-225 of Lehninger, 4th edition.
15th Class - Tues. 10/16/07 Dr. Thorpe for the remainder of course
Posted today: Problem set #6 answers.
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