Biochemistry 102a Fall 2014
Course Information
Lectures: M, W, Th 11:00-11:50 am; Volen 106
Instructor: Jeff Gelles (jeff@brandeis.edu; 781-736-2377; office: Kosow 208)
TA: Sean Guo (sguo@brandeis.edu; 315-825-1701)
Course materials on LATTE: https://moodle2.brandeis.edu/course/view.php?id=1579
What is the course about?
Understanding biological phenomena often comes down to comprehending the structures of the
molecules that participate in biochemical processes and the ways that these molecules work and
interact. Biochemistry textbooks are packed to the brim with such information, but where does
this knowledge come from in the first place? A great deal of our knowledge about biochemical
processes comes from just two basic types of laboratory experiments. First, we explore the
mechanisms of biochemical reactions by measuring the rates of various reaction steps. Second,
we infer the structures and behavior of biological molecules from the ways that they interact
with electromagnetic radiation. All such experiments involve making and interpreting
quantitative chemical and physical measurements on biochemical systems.
This is not a laboratory course, nor will it teach the details of how to use specific techniques.
Instead, the course covers basic principles that underlie a range of quantitative biochemical
experiments. Many of these principles arise from physical chemistry, and their applications to
real systems are worked out via mathematics. The aim here is to equip students with some of the
basic attitudes, approaches, and knowledge they will require to read, critically evaluate, and
ultimately contribute to original research literature in macromolecular biochemistry and
biophysics.
Another purpose of this course is to gain experience with mathematical methods in common use
in the quantitative treatment of biochemical problems – linear differential equations, concepts of
probability, statistics, stochastic processes, Fourier series. Students have seen most of these
before but usually have not had much practice actually using them. My object here is not to
torture students but rather to empower them by teaching a few of these tools and demystifying
them so that when they are encountered in the biochemical literature later on, they will be seen as
useful friends rather than as obscure tormentors.
See the separate Schedule and Course Outline for a more detailed list of the topics to be covered.
Required Preparation
The course requires knowledge of basic biochemistry at the level covered in a good introductory
college biochemistry course (e.g., BCHM 100). I will assume that you already are familiar with
fundamental chemistry concepts like Gibbs free energy and chemical equilibrium and that you
have had at least some previous exposure to basic chemical kinetics. A calculus-based
introductory physics course is an essential prerequisite. You should be very, very familiar with
the properties of common mathematical functions such as polynomials, logarithms, exponentials,
trigonometric functions and vector algebra. You must also to be able to differentiate and
integrate with ease and also to apply calculus to the solution of simple physical problems.
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Readings
The course readings come from a variety of sources including journal articles and various
textbooks. Two of the texts used are:
Fersht, A. (1999). Structure and Mechanism in Protein Science: A Guide to Enzyme
Catalysis and Protein Folding. New York, WH Freeman.
Berg, H. C. (1983). Random walks in biology. Princeton, N.J., Princeton University Press.
Both of the books are excellent reference books that are useful for any biochemist or biophysicist
to have at their desk. However, the course only uses a few small sections from each; these and
the other readings will be posted on LATTE. You should also have available an introductory
biochemistry text handy in case you need to refresh your memory of some of the background
material.
Course Organization
Problem sets. Much of the material covered in the course cannot really be understood just by
listening to me jabber on about it; you have to try it out for yourself. For that reason, the
problem sets are the most important part of the course. There will be problem sets over the
course of the semester. These must be turned in at the end of the lecture on the due date. I will
comment on them and return them, but the comments are merely for your information; they have
little effect on your grade for the course. I will not look at problem sets turned in after the due
date. Do not hesitate to collaborate with other students on the problem sets if you feel that this
will help your understanding of the material. Solutions will be posted on Latte.
Lectures. See the attached course schedule for dates of lectures. Class starts promptly at
11:00am. I usually begin each lecture by summarizing the most important point to be discussed,
so come on time. You are welcome to take notes with tablets or computers if you like. Please be
considerate of the other students by using these devices during lecture only to take notes. Other
uses (e.g., email) will be a distraction to people sitting nearby.
Recitation section. Sean will hold weekly meetings in which he will challenge students with
additional problems, which they will work on individually or in small groups and then
immediately discuss solutions. He is also available to provide help on problems sets and
clarification of lecture material either during the recitation (if time permits) or at other times.
We will schedule the recitation meetings at a time that does not conflict with other academic
commitments of any registered students.
Questions. I welcome your questions and discussion both in and out of the lectures. I try to
arrange my schedule so that I'm free right after lectures, so that is often a convenient time to talk.
You can also call or email to set up an appointment to talk with me outside of class. You are
also welcome to come by my office/lab any afternoon if you would like to talk to me. If I cannot
talk to you immediately when you come by, I will set up an appointment to help you later.
Exams. There will be three exams, two 50 minute midterm exams held during regular class
hours (see course schedule) and a final exam given during the exam period at a date and time set
by the Registrar. Exams are "closed book"; you may not consult any notes or other reference
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materials during the exam. If you miss an exam, you will receive a failing grade. As it is
essentially impossible to prepare two equivalent exams in this subject, no makeup exams will be
given for any reason. In exceptional circumstances in which a student is absent from an exam
due to a documentable emergency beyond the student’s control, an oral exam will be given. Any
student requiring special academic accommodations in the exams or lectures should make
arrangements immediately upon starting the course; see the Brandeis University Bulletin for
details.
Grades. Final grades will be determined based on exam scores and your class participation
(which includes completing problem sets).
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Biochemistry 102a Fall 2014 -- Schedule and Course Outline
Date
Thu Aug 28
Mon Sep 1
Wed Sep 3
Thu Sep 4
Mon Sep 8
Wed Sep 10
Thu Sep 11
Mon Sep 15
Wed Sep 17
Thu Sep 18
Mon Sep 22
Tue Sep 23
Wed Sep 24
Thu Sep 25
Mon Sep 29
Wed Oct 1
Thu Oct 2
Mon Oct 6
Wed Oct 8
Thu Oct 9
Mon Oct 13
Wed Oct 15
Thu Oct 16
Mon Oct 20
Wed Oct 22
Thu Oct 23
Mon Oct 27
Wed Oct 29
Thu Oct 30
Mon Nov 3
Wed Nov 5
Thu Nov 6
Mon Nov 10
Wed Nov 12
Thu Nov 13
Mon Nov 17
Wed Nov 19
Thu Nov 20
Mon Nov 24
Wed Nov 26
Thu Nov 27
Mon Dec 1
Wed Dec 3
Thu Dec 4
Mon Dec 8
Planned Lecture Topic (may change!)
Single molecules in action: Microscopic chaos, macroscopic determinism.
No classes (holiday)
The lightbulb distribution. The pdf.
Experimental single ion channel measurements. Derive the pdf for a single molecule.
Experimental single molecule pdfs by light microscopy. Theoretical single-molecule survivor function.
Ensembles in action: What is a mechanism? Rate constants. Relationship between mechanisms and rate
equations.
Rate equations. Analytical solution of rate equations.
Computational execise 1 - Numerical integration of rate equations
What goes forward must go backward. Reversible reactions and microscopic reversibility. Ensemble kinetics
experiments
Reactions in sequence
Enzyme kinetics: Steady states. Initial rate conditions. Solution of the Briggs-Haldane mechanism.
Meaning of the steady-state kinetic parameters
Pre-steady state kinetics. Burst kinetics.
No classes (holiday)
More burst.
Diffusion and capture: Macroscopic diffusion. Fick's 1st law. Steady state diffusion. Time-dependent
Random walk model of diffusion. Overcoming transport problems in large cells. Stokes Law.
Einstein's derivation of Fick's law. Diffusion limited reaction rates.
Midterm Exam 1
No classes (holiday)
Computational execise 2 -- Monte Carlo simulation of random walks
How fast can a reaction be? Smoluchowski limit.
Diffusion and capture. Reduction of dimensionality. Sliding on DNA. Sliding on microtubules.
Computational exercise 3 - Monte Carlo simulations of single-molecule reactions
Chromatography and Sedimentation: Principles of molecular separation. Countercurrent distribution.
Binomial distribution. Partition chromatography.
Gel filtration. Gel filtration measures D, not M. Movement of molecules in a force field. Viscous drag. EinsteinSmoluchowski relation.
Sedimentation velocity. Density gradients and rate zonal sedimentation. Analytical ultracentrifuge and moving
Sedimentation to equilibrium. Determining protein molecular weights II.
Molecules and radiation: An overview of quantum mechanics from 30,000 feet. Wavefunctions, states,
and energies.
Absorption and emission of photons by molecules. Digression-blackbody radiation. Stimulated and spontaneous
emission. Einstein's golden rule.
Absorption spectroscopy: Transition dipoles and dipole strength. Beer-Lambert law. Introduce
fluorescence
Fluorescence spectroscopy: Radiative and non-radiative decay. Lifetimes and quantum efficiency.
Detection applications.
Midterm Exam 2
Fluorescence polarization methods. FRAP. Polarization applikcations.
FRET. FRET Applications.
X-ray diffraction and crystallography: Overview-from crystal to atomic structure
Adding waves.
How the diffraction pattern gets its spots. Diffraction from a duck.
Duck plus goose diffraction. Laue condition.
No classes (holiday)
No classes (holiday)
Diffraction in three dimensions. Bragg's law. Miller indices.
Fourier transforms.
Computation exercise 4 -- Fourier transforms and Fourier filtering
The phase problem and how to solve it.