Structural Biology/ Biochemistry 241:  Biological Macromolecules    3 Credits

MWF 1:00 – 2:30   Room M112



Course Description


      To truly understand biological processes we must understand the macromolecules that carry out biological function. Regardless of one's particular areas of research, this knowledge allows better design and evaluation of experiments and deeper appreciation of the essence of biology. This course provides a rigorous background that will allow students to glean information from protein structures and to use and evaluate thermodynamic and kinetic concepts to understand biological function.


Concepts of thermodynamics, molecular forces, and kinetics of enzymatic and diffusional processes will be introduced and related to their practical application in experimental design and interpretation.  Principles of protein structure, packing and protein•ligand interactions will be developed through lectures, discussions and problem sets.  The use of these concepts to understand biological function and the level of individual molecular interactions and at the level of complex processes will be demonstrated through case studies from the literature.


Course Director: Bill Weis


Teaching Assistants:

Dan Kraut (dkraut@stanford)

            Office hours Thursdays from 4-6 in Beckman B477 (5-6763)

Stefan Larson (smlarson@stanford)

Office hours Tuesdays from 3-4:30 in Keck 316

Rebecca Piskorowski (rapisko@stanford)

            Office hours Wednesdays from 5-7 in Beckman B177 (3-7557)


Course Instructors:

Steven Block                                       phone: 724-4046         e-mail: sblock@stanford

Dan Herschlag                                    phone: 723-9442         e-mail: herschla@cmgm

Karla Kirkegaard                                 phone: 498-7075         e-mail: karlak@stanford

Joseph Puglisi                                     phone: 498-4397         e-mail: puglisi@stanford

Bill Weis                                             phone: 725-4623         e-mail: bill.weis@stanford


Course Format


           Lectures will be scheduled for 80 min, but lecturers are encouraged to not fill all of this time, to leave generous time for questions and for ensuring that the important, new concepts are conveyed to students at all levels


           There will be five problem sets through the course. They are due at the start of class on the specified day. The final problem set will entail describing a molecular approach to a problem of interest to you.


           Grades will be based solely on these problem sets.


           Notes will be handed out at the start of each lecture.


           Students are encouraged to ask questions at the beginning and throughout each lecture. Ample time has been allotted for questions within the schedule.


           Do not hesitate to contact any of the instructors or the TA with any questions related to the course and material covered.



Recommended (available at Stanford Bookstore):

Random Walks in Biology                                          Berg                                       

Proteins: Structures and Molecular Properties            Creighton

Structures and Mechanism in Protein Science             Fersht


On Reserve at Lane Library:

1. Introduction to Protein Structure                                         Branden &Tooze

2. Biophysical Chemistry                                                        Cantor & Schimmel

3. Physical Chemistry                                                             Eisenberg & Crothers

4. Physical Chemistry                                                             Tinoco, Sauer, and Wang       

5. Catalysis in Chemistry and Enzymology                             Jencks                                    


The recommended texts are also on reserve.


Lecture Schedule


Date                   Topic                                             Lecturer   Problem Sets

Sept 26 (Wed)             I. Introduction to Thermodynamics &            

    Molecular Forces                                        Puglisi            

Sept 28 (Fri)                            cont'd                                                   Puglisi             #1 out

Oct 1 (Mon)                            cont'd                                                   Puglisi

Oct 3 (Wed)                            cont’d                                                  Puglisi


Oct 5 (Fri)                   II. Protein Structure                                         Weis                #2 out       #1 due

Oct 8 (Mon)                            cont'd                                                   Weis

Oct 10 (Wed)                          cont'd                                                   Weis

Oct 12 (Fri)                             cont'd                                                   Weis

Oct 15 (Mon)                         cont’d                                                  Weis


                                    III.Rates of Biological Processes

Oct 17 (Wed)                          A. Diffusion and Biology                    Block               #3 out      #2 due

Oct 19 (Fri)                                         con’td                                      Block

Oct 22 (Mon)                         B. Enzymes: basic concepts of kinetics,

Catalysis & energetics                         Herschlag       

Oct 24(Wed)                                       cont’d                                      Herschlag

Oct 26 (Fri)                                         Kinetic simulation workshop  


Oct 29 (Mon)                                      cont’d                                      Herschlag        #4out      #3 due

Oct 31(Wed)                                       cont'd                                       Herschlag

Nov  2 (Fri)                                         cont’d                                      Herschlag

Nov 5 (Mon)                                       cont’d                                      Herschlag

Nov 7 (Wed)                                      cont’d                                      Herschlag


Nov. 9 (Fri)                 IV. Allostery/Molecular transducers                Block               #5 out      #4 due

Nov 12 (Mon)                                     cont’d                                      Block


V. Protein.  Protein Interaction and

Nov 14 (Wed)                         Biochemical approaches                      Herschlag

Nov 16 (Fri)                                        cont’d                                      Kirkegaard

Nov 19 (Mon)                                     cont’d                                      Kirkegaard


Nov 21 (Wed)                                                                                     TBA


Nov 23 (Fri)              Holiday                                                                                                        

Nov  26 (Mon)                                    cont’d                                      Kirkegaard      #5 due

Nov 28(Wed)              VI. Single molecule approaches                      Block

Nov 30 (Fri)                                        cont’d                                      Block  

Dec 3-7(Mon)             Student research presentations                                                                       

Dec 10 - 14                 FINALS WEEK


Homework set 2:


  1. Download the SwissPDB viewer to your machine. Follow the links on the site for the tutorial. The lysozyme coordinate set is 1HEW.pdb


B.   The coordinate files for the homework are: rama.pdb 1dfj.pdb 1flv.pdb 2bnh_sup.pdb mbp_trimer.pdb 1D2N.pdb


Homework set 4a (Kinetic Modeling):


You may find it useful/necessary to download the class handout (containing the problem set), a short guide to modeling with Berkeley Madonna, the entire BM users guide, and the Lorsch & Herschlag article necessary to complete the homework.


Herschlag lecture notes 1

Katrin's Berkeley Madonna lecture notes



So do we understand how enzymes work? (David Blow)

Structural and Thermodynamic Strategies for Site-Specific DNA Binding

Proteins. (Linda Jen-Jacobson)

Pyle1990 (scanned in)

Pyle1991 (scanned in)