CHEM 732 Advances in Macromolecular Structure Tuesday ...

CHEM 732 Advances in Macromolecular Structure
Tuesday/Thursday, 8:00 – 9:15, Kenan 121
Gary Pielak is the instructor for first two-thirds of course.
Office hours: 4:00-5:00 PM Friday in Kenan 748 or by appointment.
*Order ACS Style Guide (second edition, eBay ~$5) on day of first lecture.
*Download pdf files of the papers cited on page 3 before second lecture.
*Begin readings on page 3 before second lecture.
*This class is an experiment. We will discuss the topics described on
page 3. Be prepared to take part in discussions and ask questions.
Lecture Schedule
Tuesday 08-24 Start Topics on page 3. Order ACS Style Guide.
Download pdfs. Will Monteith lectures on enzymes.
Thursday 08-26
Andrew Miklos lectures on standard states and Eyring.
Tuesday 08-31 Continue topics on page 3…
Thursday 09-02
Tuesday 09-07
Thursday 09-09
Tuesday 09-14
Thursday 09-16
Tuesday 09-21
Thursday 09-23
Tuesday 09-28
Thursday 09-30 BBSP students talk about choosing a lab. Will
Monteith will lead discussion.
Tuesday 10-05 Nobel Prize in Physiology or Medicine announced 10/4
Thursday 10-07 Nobel Prize in Chemistry announced 10/6

CHEM 732 Syllabus, page 2
Tuesday 10-12 no class, University Day
Thursday 10-14
Student led session
Tuesday 10-19
Thursday 10-21
no class, fall break
Tuesday 10-26 Student led session
Thursday 10-28
Pass out take-home examination
Grading. Take home examinations.
Gary’s Exam is due Thursday, November 4, and accounts for 67% of grade
Letter grades are assigned as described below.
av is the class average. sd is the standard deviation of the mean.
H >[av + (1.75 x sd)]
P+ >[av + (1.50 x sd)]
P >[av - (0.50 x sd)]
L >[av - (1.50 x sd)]
F

CHEM 732 Syllabus, page 3
Why study enzymes
Topics
pH and the Henderson-Hasselbalch Equation. Any biochemistry text.
Steady State Enzyme Kinetics
Any biochemistry textbook, but Fersht [(1999). Structure and mechanism in
protein science: a guide to enzyme catalysis and protein folding. New
York, Freeman] gives a nice overview.
Deriving the Michaelis-Menten equation
What do Km and kcat mean
Standard state free energies. Eyring equation. Any p-chem text.
How to Review and Write a Paper: The ACS Style Guide, 2 nd
edition
Enzyme Proficiency
What is it
Most Proficient Enzyme Known
Enzyme evolution—hypotheses and neo Darwinism
Lewis CA, Wolfenden R. 2008. Uroporphyrinogen decarboxylation as a
benchmark for the catalytic proficiency of enzymes. Proceedings of the
National Academy of Sciences 105: 17328
Wolfenden, R.V. (2010) THERMAL COLLAPSE OF THE TIME REQUIRED FOR
PRIMORDIAL CHEMISTRY AND THE EVOLUTION OF BIOLOGICAL CATALYSTS, submitted
(I will supply this pdf.)
False Starts at Enzyme Design
Alan Fersht: Trust
Altamirano MM, Blackburn JM, Aguayo C, Fersht AR. 2000. Directed evolution
of a new catalytic activity using the β-barrel scaffold. Nature 403: 617
Altamirano MM, Blackburn JM, Aguayo C, Fersht AR. 2002. retraction:
Directed evolution of new catalytic activity using the [alpha]/[beta]-
barrel scaffold. Nature 417: 468
Homme Hellinga: Error analysis & mentor-student interactions
Dwyer MA, Looger LL, Hellinga HW. 2004. Computational design of a
biologically active enzyme. Science 304: 1967
Dwyer MA, Looger LL, Hellinga HW. 2008. Retraction. Science 319: 569
Hayden EC. 2008. Chemistry: Designer debacle. Nature 453: 275
Hellinga HW. 2008. In the wake of two retractions, a request for
investigation. Nature 454: 397

CHEM 732 Syllabus, page 4
A Successful Design
Röthlisberger D, Khersonsky O, Wollacott AM, Jiang L, DeChancie J, Betker
J, Gallaher JL, Althoff EA, Zanghellini A, Dym O, Albeck S, Houk KN,
Tawfik DS, Baker D. 2008. Kemp elimination catalysts by computational
enzyme design. Nature 453: 190
Or Was It
Holfelder F, Kirby AJ, Tawfik DS. 1996. Off-the-shelf proteins that rival
tailor-made antibodies as catalysts. Nature 383: 60
Lassila JK, Baker D, Herschlag D. 2010. Origins of catalysis by
computationally designed retroaldolase enzymes. Proceedings of the
National Academy of Sciences 107: 4937
Maybe the best was done years ago
Abrahmsen L, Tom J, Burnier J, Butcher KA, Kossiakoff A, Wells JA. 1991.
Engineering subtilisin and its substrates for efficient ligation of
peptide bonds in aqueous solution. Biochemistry 30: 4151
What makes a good drug Lipinski rules of five
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and
computational approaches to estimate solubility and permeability in drug
discovery and development settings. Advanced Drug Delivery Reviews 1997;
23: 3-25.
Artificial life
And man made life, The Economist, May 20th 2010
Pennisi E. Synthetic Genome Brings New Life to Bacterium. Science;328:958-
959.
Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang R-Y, Algire MA, Benders
GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R,
Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi Z-Q, Segall-
Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, III, Smith HO, Venter JC.
Creation of a Bacterial Cell Controlled by a Chemically Synthesized
Genome. Science;329:52-56.