- Get familiarized with the techniques of biomolecular visualization: understand how biomolecules are represented, learn how to select the right representation for the particular aspect that we want to study in each case, and, eventually, realize that a structure can explain function.
- Learn to apply a state-of-the-art molecular visualization program for your own projects. That is why we use the stand-alone program PyMOL here, instead of embedding graphics directly in the tutorial.
2.- Tutorial Structure
- The tutorial is divided into six independent and progressive modules that introduce the structures of biomolecules or biomolecular complexes which exemplify a wide range of biochemical and biological concepts and theories.
- Each module aims at different objectives with respect to biochemistry and the use of PyMOL. The level of complexity of the tasks increases with the progression of the tutorial
- Each module (page) is divided into two columns. The main text, with biochemical explanations and references to PyMOL menus, can be followed on the right column, while the left column is devoted to the interaction with PyMOL
- The “theoretical background” sections discuss the concepts that are exemplified and give references to two biochemical textbooks. Interested users can use the examples as starting points either for the recapitulation of biochemical concepts or for gaining deeper insight into biochemistry.
- The referenced textbooks are 1) “Lehninger Principles of Biochemistry” by David Nelson and Michael Cox (Fourth edition, 2005, Freeman and Company, New York), abbreviated “NC”, and 2) “Biochemistry” by Donald and Juith Voet (Third Edition, 2004, John Wiley and Sons, USA), abbreviated “VV”. Similar chapters are found in most or all other biochemical textbooks.
- A prerequisite for understanding the interaction of biomolecules with ligands, signaling molecules or substrates is the knowledge about the monomeric building blocks that biomolecules are composed of, e.g. amino acids, nucleotides, and fatty acids. The basic concepts of the properties of water, acids/bases and buffers, about solubility and hydration, covalent bonds and non-covalent interactions should be known. These informations are usually covered in the introductory chapters of biochemistry, cell biology, microbiological and physiological text books (NC 1, 2, 3.1 – 3.2, 3.4 – 3.5; VV 2, 3, 4, 5.1)
3.- How does it technically work?
- The Protein Data Bank (PDB).
It is a
repository for 3-D structural data of biomolecules, typically
determined by X-ray crystallography or NMR spectroscopy. Data is
submitted from laboratories around the world and can be
for free at http://www.rcsb.org
The biomolecules studied in this tutorial are obtained from
this repository. More about
- PyMOL is
an open-source molecular visualization program. It is
well suited to producing high quality images of small molecules and
biomolecules. http://pymol.sourceforge.net/ More
- Mozilla Firefox is a free web
should be reading this text in it. Other web browsers might also work
for this tutorial, but they have not been tested. http://www.mozilla-europe.org/
- The PyMOL handler is a small application developed at the Molecular Bioinformatics Laboratory - J.W. Goethe University Frankfurt. It establishes the communication between the web browser and PyMOL and is key for this tutorial.
The following scheme illustrates how the 4 components interact with each other. The user will follow the tutorial at the Firefox window (right). Clicking on links has an effect on the PyMOL window (left), which is achieved by connecting Firefox and PyMOL through the handler (see below). If a biomolecular structure is needed, PyMOL will download it from the PDB.
4.- Installation of the required componentsIn order to pass commands to PyMOL from the web browser, a client program is needed. In addition your browser (note that only FIREFOX is supported) has to be configured to handle files with the extension .pymolrpc with that client.
In the following steps, the installation procedure of the required components is explained. Each step is illustrated with what you should be seeing in your computer as you proceed with the installation.
Step 1. Install Mozilla Firefox
|Download the client from here. After clicking, a window dialog similar to the one on the right will pop up. Choose "Save to Disk". Once the download is completed, unzip the file.|
After unzipping you will see the contents of the folder. These are the files shown on the right. The program (which is the PyMOL handler) we need in a minute is called runpymol.exe. For everything to work properly, the config.ini file might need editing to point to the PyMOL executable. Open it with the Windows notepad, and you will see something like the following picture.
Edit that line, if it is not correct, so that it is specifying where PyMOL is installed in your computer.
NOTE that in a standard installation of PyMOL, on a Windows system in German, you will find that PyMOL is installed under: C:\Programme\DeLano Scientific\PyMOL\PyMOLWin.exe
Step 4. Associate the PyMOL handler with files with "pymolrpc" extensions
|For the final step, we will launch PyMOL just from
here. Click here to
After clicking the link to "launch PyMOL", Firefox will ask (see right!) what to do with a file called "something.pymolrpc"
Choose "Open with" and browse your file system to find the runpymol.exe you just downloaded and unzipped. (See the figures below)
PyMOL will be automatically started, if you just clicked the "launch PyMOL" link. Wait until PyMOL completely starts and you see a message like the one shown in the figure below. Once you observe that PyMOL is running, click OK and the program will try to establish a connection.
Wait until the word "Ready" appears on the screen. From this point everything will run smoothly.