Teaching Resources in Biochemistry:

Jason Kahn, University of Maryland College Park.
Disclaimer: I know this area could be better organized. I know some of the content is out of date. It will gradually improve. Let me know if specific things that you need are broken.

Nucleic Acid Sequence, Stability, Structure, and Dynamics

Tools and Tutorials for Molecular Structure

Excel spreadsheets for modeling simple chemical and biochemical principles.

Matlab programs for modeling simple chemical and biochemical principles.

Protein domains and (mis)folding overheads.

Student posters (very old)

Rasmol/Chime/Jmol installation and use

Biochem 461/463-oriented materials (protein structure and allostery)

PDB files of nucleic acids and protein-nucleic acid complexes

Biochemistry 465 and 661/662 and the old 674

Collection of exams

Literature Searching and EndNote/Papers Hints (Biochemistry 677)

TEDxUMD talk on teaching philosophy

Nucleic Acid Sequence, Stability, Structure, Dynamics, Enzymology

• RNA/DNA structure
  1. The Watson-Crick base pairs. Interchangeability within a helix, (pseudo)symmetry axes.
  2. Hand-drawn sketches of the geometric origin of helicity and DNA microheterogeneity/bending.
  3. How a helix grows from a base pair.
  4. Jmol visualization of B-DNA and A-RNA.
  5. Why there's no B-form RNA.
  6. Jmol visualization of tRNA.
  7. Structure of a psoralen crosslink.
  8. Rasmol on Tertiary structure in tRNA.
  9. Sketch of RNA secondary and tertiary structure.
  10. Here are web sites for RNA structure, function, folding:
      • http://www.tbi.univie.ac.at/~ivo/RNA/
      • http://www.bioinfo.rpi.edu/~zukerm/rna/
      • http://www.imb-jena.de/RNA.html
• DNA Flexibility and Bending
  1. Sketch of DNA bending.
  2. Sketch of DNA flexibibility and cyclization.
  3. Wormlike coil model for DNA.
  4. Informal notes on DNA topology.
  5. Sketch of the definition of linking number.
  6. Twist-writhe interconversion in DNA supercoiling.
  7. Sketch of the shapes assumed by supercoiled DNA.
• Nucleosomes and Chromatin
  1. Basic nucleosome structure.
  2. 30 nm fiber structure
  3. Tetrasome structure (model for 30 nm fiber)
  4. Histone code proposal
  5. Patterns of chromatin modification
• Bioinformatics
  1. Intro to BLAST (from Chuck Delwiche).
  2. Web site for tutorials on bioinformatics.
• Mathematics and Simulations of Hybridization, protein-DNA binding, kinetic partitioning.
  1. Page of math on simple binding curves. And here is a simple spreadsheet illustrating the simple Ybar = P/(P+Kd) binding isotherm.
  2. Spreadsheet and mathematics for two-state hybridization and melting curve predictions.
  3. Detailed discussion of proofreading through kinetic partitioning.
• Processes
  1. DNA polymerase structures, mechanism, active sites.
  2. T7 DNA polymerase structure and fingers closing.
  3. Organization of the Pol III holoenzyme complex.
  4. PDF of images of the trombone model, DnaA structure, and the initiation of replication.
  5. (External, high tech.) Animations of the pol III replisome.
  6. RNA Polymerase cartoons and structures.
  7. Notes on RNAi.
  8. Sketch of replication-mediated homologous recombination in E. coli.
  9. Sketch of recombination-mediated repair of collapsed replication forks in E. coli.
  10. Movies of the first step of translation from molecular dynamics. And the more lighthearted, but still informative, 1971 dance version of the whole process of translation.The movie was sponsored by the late Kent Wilson, of UCSD.

Tools and Tutorials for Molecular Structure:

This file links to a variety of small tutorials/examples focusing on visualization of biomolecules in three dimensions, using the program RasMol.

• Jmol-based tutorial on steroid/retinoid hormone receptor binding to DNA.
• The nucleosome, both here and at the Molecule of the Month at the PDB.
• Installation directions for Rasmol/Chime.
• Biochemistry 461/463: Tutorials on
  • The Ramachandran diagram and conformational analysis.
  • Protein secondary structural elements.
  • The TIM barrel and other prototypical tertiary folds.
  • Hemoglobin as an example of tertiary and quaternary conformational changes accompanying oxygen binding.
• Biochemistry 465, 661/662, and old 674:
  • Structures of nucleic acids and protein-nucleic acid complexes.
  • Biochemistry 465, 661/662, and old 674: Tutorial on A and B form DNA and RNA structures.
  • Biochemistry 465, 661/662, and old 674: Tutorials on protein-DNA and protein-RNA complexes.
• Other web-based educational structure resources:
  • Loren Williams' structure tool at Georgia Tech.
  • A huge list of tutorials maintained by Eric Martz at UMass Amherst.
  • Will McClure's site at Carnegie Mellon is one of my personal favorites. Requires Chime.

A very brief note on philosophy

Note: perhaps I flatter myself, but if you link to this page or otherwise make substantive use of the content, please let me know and/or link/give credit appropriately. Suggestions are always welcome. The creation of this content was part of the educational part of an NSF Career Award Proposal.

Rasmol/Chime/Jmol installation and use

Update 2005: The free Jmol viewer appears to be a viable replacement for most of Rasmol and especially Chime.

To view structures in PDB (= Protein Data Bank) format you need a program which understands PDB. The free options in most common use are RasMol and Chime. Rasmol is a stand-alone program available for Mac, Windows, and Unix platforms. Chime is a plug-in which as of this writing works only with recent versions of Netscape. The Protein Explorer is essentially an environment used to run Chime more intuitively, with a lot of typical commands pre-loaded. It makes extensive use of javascripts for communication between Chime and the user.

To view structures on/from the Web, you have to configure your browser to launch a PDB viewer program. To do this, you have several options. This server (www.biochem.umd.edu) supports the experimental mime type chemical/x-pdb. If you configure your browser correctly (see below), you can bring up a pdb viewer (either Rasmol or Chime) directly upon clicking on a PDB file link. Otherwise, you will be asked to save the file and can then read it in to a viewer (Rasmol) from outside your browser. On some platforms (e.g. Silicon Graphics, probably other X-windows), you need to tell Netwscape to open a shell window which then in turn runs Rasmol, otherwise the command window will not appear (Netscape intercepts the application's desire to open a window). One option that should always work is to launch Rasmol on its own, save the pdb file as text (download by holding the mouse down on the link (Mac) or using the alt key (SGI)), and then open the pdb file from within Rasmol.

There is an excellent resource on Rasmol and Chime, including pointers to download locations and many examples, at U Mass. This site showcases much more sophisticated presentations than are provided here, but at some cost to simplicity and interactivity. The Protein Explorer is emphasized at the site.

You can get the Chime plug-in to display structures from within Netscape from MDLI . IMHO (= in my humble opinion, for "newbies"), Rasmol is better, especially if you have a pre-1994 computer. Nothing can crash a computer like Netscape, esp. w/ plug-ins, and Chime doesn't seem to provide a user-accessible command line, although it can read more file formats and is apparently better for advanced scripting within Web pages. Rasmol can be run on its own after you have quit Netscape or whatever and re-connected your phone line, and the command line gives you more control and immediate feedback. You can even just ftp the pdb file and run Rasmol without running a browser at all, but any computer that can't run Netscape will probably choke on any complicated Rasmol work.

For more rasmol, other PDB viewers, and a great deal more, see The NIH Guide to Molecular Modeling . It's difficult navigating but there's a wealth of information there.

Configuration directions for using Rasmol and Chime:

1. If it isn't already available, get Rasmol (it's freely downloadable) and install/compile it on your computer.
2. For Mac/SGI Netscape, set helper applications or plug-in choices under "Options/General/Helpers", such that the chemical/x-pdb file type or any file that ends in ".pdb" is opened by Rasmol. To enable the use of the command window under X-windows, use the line below as the "helper application" (thank you very much to Roger Sayle for this info):
   xterm -e rasmol %s
   For Windoze or Internet Explorer, Microsoft probably lets you do something similar but you're on your own as to exactly how.

   If you install the Chime plug-in, you choose to launch the plug-in essentially as above. You can go back and forth if you wish -- I have both installed but usually use RasMol.

   Some UNIX setups may require you to change your .mailcap file. Include the line:
   chemical/x-pdb ; rasmol %s
   If you install Chime, it will modify the .mailcap file or otherwise take over.

Biochem 461/463-oriented materials:

If you are using Netscape/Rasmol as above, download the pdb file first and thereby launch Rasmol. Then go to the appropriate command file and cut and paste line by line or larger chunks from Netscape to the command line in Rasmol (you may be able to choose "Paste" even when the structure window is uppermost).

Here is a rather arcane spreadsheet rationalizing why irreversible steps in a pathway are the right places to control flux.

Structures of amino acids and proteins

Protein conformational analysis: the Ramachandran plot

• The Graphical table, with phi/psi angles and links. Note this is a very large page (~1 MB) and will take a while to load.

Alpha helix and beta sheet structures

The files below are provided as examples of idealized secondary structures.

NEW: These little tutorials have been recoeed for jmol but may not have been fully debugged.
Here is the alpha helix.
Here is the same alpha helix in reality in the GCN4-DNA co-crystal.
Here is the beta sheet.
Here is the beta sheet in the protein tendamistat .

The .txt files below are lists of Rasmol commands. On a Mac or SGI, you can cut-and-paste commands into the command window as I do in class -- take chunks delimited by # signs or pause statements, or go line-by-line. Pasting also works in newer versions of Jmol, and it uses essentially the same command language. On Windows, pasting doesn't work and you will have to save the file as a script and then "script file_name" to run it. You will need to give the complete path.

The .scr file is a Rasmol script which recreates a particular view. The .pdb files are the actual molecular data files, essentially xyz coordinates of the atoms. These are just text files -- go ahead and look.

• The idealized alpha helix .pdb file.
• The idealized alpha helix display command file ideal_alpha.txt.
• The final picture of a small alpha helix chunk.
• The same helix in the context of GCN4, .pdb file.
• The idealized beta sheet .pdb file.
• The idealized beta sheet commands ideal_beta.txt.
• Gif image of what you get after issuing the above commands.
• The protein tendamistat .pdb file.
• The tendamistat .txt command file, including directions to run the script below.
• The Rasmol script tendisp.scr for tendamistat. A "script" is different from a list of commands. It recreates a particular view rapidly and efficiently, but you often don't quite know how. The script file apparently must be in the same directory as the rasmol program in order to run. Download it, "save as", move the file to the same directory as the Rasmol program, and then run the command file above via the command line. Otherwise, you can edit the .txt file to include the full path name of the tendisp.scr script.
• Tendamistat gif file exported from Rasmol.

Protein supersecondary and tertiary structure example: TIM et al.

• The PDB file (2ypi.pdb) for TIM, with substrate analog 2-phosphoglycolate. Or click here to download as text.
• The Rasmol commands for displaying one of the two molecules in the PDB file.
• A gif file showing approximately what you should get after running the script commands.

• The PDB file (2mhr.pdb) for myohemerythrin.
• The Rasmol commands for displaying a simple secondary structure representation. The second part of the script lets you "slab" through the molecule to see how crowded the apparently rather open core really is.
• A gif file showing approximately what you should get after running the script commands.

• The PDB file (1tta.pdb) for transthyretin.
• The Rasmol commands for displaying a simple secondary structure representation, using the same color coding as for myohemerythrin.
• A gif file showing approximately what you should get after running the script commands.

• The PDB file (2yhx.pdb) for the "open" form of hexokinase, with a bound inhibitor of glucose binding (OTG). The coordinates of the OTG were used to model the position of glucose below.
• The PDB file (1hkg.pdb) for the "closed" form of hexokinase. Note glucose was not visible in the original X-ray structure, and the secondary structure is not as refined.
• The Rasmol commands for displaying a simple secondary structure representation, using the same color coding as for myohemerythrin.
• Images showing approximately what you should get after running the script commands for the closed and open form.

Quaternary structure and allostery

• The deoxy form. Note the relatively large central cavity, and domed hemes, as well as the relative positions of the end of the beat subunit FG corner (His97) and the alpha subunit CD corner (Thr41-Pro44).
• The oxy form, modified from the original pdb to show all four subunits. Note the relatively small central cavity, and flattened hemes, as well as the shift of the end of the beta subunit FG corner (His97), which now approaches alpha Thr38. This rearrangement (and the consequent breaking of salt bridges) is part of an overall rotation of one alpha-beta dimer with respect to the other.
• This file of Rasmol commands should work for both forms.
• The side-by-side comparison shows that local (heme) changes and quaternary changes are much easier to see than the rather subtle tertiary changes which mediate the cooperativity. It may help to look at this first and then go to the rasmol files.
• Here is a spreadsheet allowing you to graph fractional saturation as a function of binding constants, R and T preferences, BPG, and so forth. Equations taken from van Holde, "Physical Biochemistry". (Download to disk using right-mouse or control-mouse, then open in Excel.)

PDB files of nucleic acids and protein-nucleic acid complexes

Biochemistry 465, 661/662, and old 674:

• Follow this link to the A and B forms of DNA and RNA tutorial directory.
• Follow this link to the protein-DNA interaction tutorial directory.
• Follow this link to the protein-RNA interaction tutorial directory.
• Here is a PDB file of tRNA. Try using Rasmol or your own favorite program to do coloring by group (to emphasize which helices stack on each other), viewing cartoons and sticks, and spacefilling residues 22 and (Boolean or) 46 and (Boolean or) 13, which form a triple base pair that holds the molecule together. Here is a result from the open-source, cross-platform program PyMol. Alternatively, here is a Jmol page that shows you most of the same things.
• 
• The structure of the nucleosome.
• Loren Williams' teaching pages at Georgia Tech have a wealth of material in a vein similar to what you will find here. Coverage is especially strong for DNA-drug and DNA-protein interaction.
• The Protein Data Bank's Molecule of the Month is often worthwhile. Here is their view of the nucleosome.