Users manual

Life may be described as a set of biochemical reactions involving substances as small as hydrogen ions up to the size of giant macromolecules. Life sciences try to explain all aspects of living nature from simple metabolic steps in microorganisms up to the generation of conscience in higher organisms. The description may be rather abstract like a chemical formula defining reactands and products with an exact mass balance. However, to gain some understanding of the mechanisms involved it is helpful to "see" the molecules at work, on an atomic scale. Work has the meaning of interactions of the electron clouds of atoms involved in chemical reactions. To "see" requires the elucidation of the structures of molecules and to find a way to display the spatial configurations or even movements accompanying the "work".

Atomic coordinates of (in July 1999) 10.000 macromolecules are available from the Protein Data Bank, other databanks hold the structures of small molecules or nucleic acids and their complexes, so many facets of biochemistry and molecular biology may be made visible. Computer programs were developed to generate high quality images of molecular structures. For the average enthusiast owning a wintel PC there is a program set allowing the interactive exploration of molecules using publicly accessible atomic data sets. The program Chime enables the generation of movies for viewing by a web browser. The spectator may step through the movies at his own pace or be guided by the author of the underlying script. In the following some conventions for the display of structures are described which ease the understanding of the molecules.

Building blocks of proteins are amino acids. Shown here is a simple one, alanine. Ala

The rotating picture to the right is a model only, symbolizing atoms as spheres and chemical bonds as rods with distances between the atoms to the same (but arbitrary) scale. The model may have different appearences according to the properties of the molecule to be emphasized. According to the provisions made by the author the user has the choice to modify the view by clicking buttons which either trigger a one-time event or toggle between different states. Please have a try:

Additionally, there is always the possibility to change the view by using the mouse: click and drag in the picture turns the molecule at will, clicking right on the mouse opens menues for near unlimited further manipulations. This may easily mess up the view. To have convenient starting positions in the scripts I introduced oblong buttons (like the "reset" above) which display the molecules in an appropiate orientation for further demonstrations. Especially in stepping back to have a second view it is a good idea to restart using this other kind of button. If the square ones are used in a nonconsecutive manner, perhaps funny views are the result of my laziness in programming all eventualities.

Most protein structures are elucidated by X-ray methods which doesn't show hydrogen atoms. Alanine thus is abstracted to something like the structure to the left. Adding another alanine turns the structure into a dipeptide

, one more to a tripeptide

. More amino acids result in a pentapeptide

, whose spatial orientation is not random, but fixed by a hydrogen bond

(turn the molecule to have a better view!). This may be carried further

to the form of a short protein. The frame to the left now demonstrates the unsuitability of this kind of modelbuilding for this (still low!) number of atoms: more abstraction is necessary. This may be achieved by omitting all atoms but the C_alpha of each amino acid and connecting these by "bonds"

. In this kind of presentation of the structure the pattern of the arrangement of the amino acids is evident

: the C_alpha-atoms are placed to form a screw thread (Latin: helix). This is a common secondary structure motiv in proteins. To highlight these motivs in graphical presentations of protein structure some conventions were introduced:

(After pressing the spin-button you may notice at the bottom of the Netscape-window the words Chime script executing... As long as this shows, all buttons are inoperative because the program is busy.)
The different ways to symbolize a protein helix may be used at will as is appropriate to demonstrate the features of a particular structure. The "trace" function is generally useful to give an overview of a protein's chain because of its high transparency.

Amino acids engaged in peptide bonds are able to adopt different patterns of hydrogen bonds. Another commonly found secondary structure element is a pleated sheet composed of amino acid strands

. The view may be simplified like that of the helix

and symbolized likewise

In the cartoon display please note the pointedness of the strand symbols, the arrows leading the way from the amino- to the carboxyterminus of the peptide.
Within the formalized presentation of a protein any special highlights are possible. So the alternating orientation of the amino acid sidechains relative to the plane of a sheet may be emphasized

The peptides shown above are part of a real protein, the enzyme lysozyme, the whole structure of which is shown to the left. There are more helices

and strands forming sheets

connected by a network of turns

A word on the use of color: any atom/amino acid/protein chain may have a color assigned by the author of a script according to her or his likes. But there are some rules and suggestions built into the program. Atoms are colored according to the cpk-scheme (proposed long ago by Corey, Pauling and Kultun), i.e. carbon light grey, oxygen red, nitrogen blue, hydrogen white, sulphur yellow, phosphorus orange, chlorine green, etc. Secondary structure elements have default colors as in the cartoon scheme to the left. Protein chains may be given colors with special meanings:

This piece of DNA is part of a complex structure involving the DNA binding protein IHF (integration host factor)

from the bacterium Escherichia coli.

Literature:
Sayle, Roger & Bissell, Andrew: In: Proceedings of the 10th Eurographics UK '92 Conference, University of Edinburgh, Scotland, April 1992 - RasMol: A program for fast realistic rendering of molecular structures with shadows
Casher, Omer et al: J. Chem. Soc., Perkin Trans 2, 1995, 7 - Hyperactive Molecules and the World-Wide-Web Information System
Richardson, Jane S.: Advances in protein chemistry 14 (1981) 167-339 - The anatomy and taxonomy of protein structure

How to use the Chime scripts in this project

From atomic coordinates to interactive graphics: a virtual molecular modelling kit