The advance of computers has made rendering of molecules in three dimensions relatively easy and common place. There are several ways one can display a model of any particular molecule and I will briefly discuss the way we are displaying them in both the GUI (client, newly installed nodes and release version 2.0) and on the webpage.

1. Stick model: Here the molecule is effectively displayed by sticks that represent bonds between atoms. The atoms themselves are not shown. The thickness of the stick can be changed to taste. This type of model is particularly useful to chemists (scientist that make these molecules) since important structural features are easily identified. Often molecules (candidates) are shown this way. The atoms are colored in a consistent manner:

C - carbon (black or grey)
H - hydrogen (white)
O - oxygen (red)
N - nitrogen (blue)

An example is given below:



Figure A: Example of a stick model.

2. Ball and stick model: This is similar to the stick model with the atom themselves being represented as balls of larger diameter than the sticks (bonds). This type of model does not yield more information than the stick model. Chemists tend to favor the stick model for its simplicity. Atoms add clutter to the picture but are esthetically pleasing to look at. This type of model is regularly used by scientists who build plastic models of molecules to obtain a better idea of the 3-D nature of the molecule they are dealing with.

Figure B: Example of a ball and stick model.

3. CPK - space filling model: CPK are the initials of the scientist that first used this type of model (Corey, Pauling, Koltun). Here the atoms are represented as overlapping spheres with diameters corresponding to their Van der Waals radius. This model gives a better sense of how crowded the space is around molecules. This type of model is not very useful to chemists since much of the structure is not visible from any perspective. There are however cases where it is important to understand what the spatial requirements are for a molecule to fit into a pocket or fit through a hole in a membrane.

Figure C: Example of a space filling model. CPK)

4. Ribbon: Proteins are very large molecules made up of repetitive subunits called amino acid residues and are referred to as hetero-polymers. The sequence of amino acid residues strung together in a long polymer is often referred to as its primary structure. This long string forms several different types of secondary structures such as alpha helices (springs), beta pleated sheets and beta turns. The highest level of organization in a protein is referred to as its tertiary structure and refers to the arrangement of various secondary structural elements such as alpha helices, beta pleated sheets and beta turns. The ribbon model of a protein shows the three dimensional arrangement secondary structural elements and is a flat ribbon like representation of the backbone of the string of amino acid residues. This type of model gives less specific detail about the arrangement of individual atoms in the structure but displays important information with regards to the tertiary structure of the protein. Often a combination of stick and ribbon models are used to display proteins. For comparison a stick model, a ribbon and stick model and a ribbon model of a protein are shown below:

Figure D: Stick model of Phosphoinositide3-Kinase



Figure E: Ribbon and stick model of Phosphoinositide3-Kinase



Figure F: Ribbon model of Phosphoinositide3-Kinase

The different secondary structural motives can be identified by their coloration:

Red - alpha helices
Turquoise - beta pleated sheets
Green - beta turns

Surface model: In particular the solvent accessible surface (i.e. The surface of the molecule as experienced by a proto-typical solvent molecule) is useful to probe the surface of a protein for pockets and crevices as potential binding pockets. Superimposed on this surface is a visualization of partial atomic charges which portraits the electronic requirements for binding in that region. The sign and magnitude of the partial charges are indicated by color and intensity respectively. The brighter the color the higher the charge.

Blue - Negative charge
Red - Positive charge
White - Neutral

This model looks similar to the CPK representation but communicates significantly more valuable information.

Figure G: Solvent accessible surface Phosphoinositide3-Kinase colored according to partial charges on solvent accessible atoms.

The surface model is most informative for binding sites and we will use this type of representation for the binding sites under investigation on all the targets. The rest of the protein (target) will be displayed as a ribbon model. This yields the most information and is visually most pleasing. An example is given below:

Figure H: Ribbon and surface structure Phosphoinositide3-Kinase.

To this "pocket" one can then add the inhibitor ( = drug candidate: molecules that inhibit a function of a protein (target) are often potential drugs). An Example is given below:

Figure I: Ribbon and Surface structure of Phosphoinositide3-Kinase with an inhibitor (Quercetin) bound in the active site.

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