Protein Investigator

The Protein Investigator

(1) Introduction
Many lab exercises use molecular visualization software that allows students to to 'see' a protein in its full 3-dimensional form and to make hypotheses about the interactions between various side chains. However, these programs do not allow students to test their hypotheses because molecular visualization software does not allow students to make changes to the protein sequence and observe their effects on the protein's structure and function.

The Protein Investigator gives students an opportunity to interactively explore protein structure and function in a simplified system. This is a highly-simplified model of protein folding. It is not intended to predict the correct structures of any proteins; it is designed to illustrate the major principles involved in that process. The important features of proteins that this software retains are as follows:

Amino acids have side-chains of varying hydrophobicity, charge, and hydrogen bonding capacity.
The amino acids a reconnected in an un-branched chain that can bend.
Hydrophobic amino acids will tend to avoid the water that surrounds the protein; hydrophilic amino acids will bind to the water.
Amino acids that can form hydrogen bonds will tend to form hydrogen bonds if they can.
Positively-charged amino acids will tend to form ionic bonds with negatively-charged amino acids if they can.
Like-charged amino acids will repel each other if they can.
Ionic interactions are stronger than hydrogen bonds, which are stronger than hydrophobic interactions.
Proteins can be folded under oxidizing (Disulfide Bonds ON) or reducing (Disulfide Bonds OFF) conditions.

Even though this software provides some important insights into protein folding, you should always keep in mind that this is an approximation. The most important "gotcha's" to be aware of are:

This program folds proteins in 2-dimensions only.
This program treats all amino acids as equal-sized circles.
This program folds the protein based on the interactions between the side chains only.
This program does not model secondary or quaternary structure.
This program assumes that all side chains with hydrogen bonding capability can bond with each other.

These simplifications are necessary for two reasons. The first is technical: it turns out to be extremely difficult to predict the full 3-d folded structure of a protein given only its amino acid sequence. As of the writing of this web page, it takes a super-computer several days to predict the fully-folded shape of even a small protein like lysozyme. Even then, the predictions don't always match known structures. The second reason is educational. As you saw in other labs, proteins are complex 3-dimensional molecules. It can be hard to find your way around when inside one. Likewise, it would be very difficult to visually compare two protein molecules to observe the effects of changes to their amino acid sequence. It would be easy to miss the forest (the forces that control protein structure) for the trees (the tiny details of the structures). For these reasons, we will use this simplification. It retains the properties of amino acids that are important in Bio 111 while being simple and fast.

You can view the help file included with Protein Investigator.

This software was written by Brian White (Biology Department; UMass Boston), Ethan Bolker (Math/CS Department; UMass Boston), and the MGX team.

(3) Downloading and Installing

In order to run the Protein Investigator, you will need the latest version of Java.

Macintosh OS 9.2 and lower does not have Java; you cannot run Protein Investigator with this OS.
Macintosh OS X has the proper version of Java built in. You can run Software Update to be sure you have the latest version.
Windows does not come with Java installed. You can download it free from this link

You can get the latest version of the Protein Investigator (Version 3.0.2 as of October 30, 2009) from the appropriate link below:

Protein Investigator for Windows
Protein Investigator for Mac OS X Note: Some versions of Mas OSX give a popup that says "Unable to Load Java Runtime Environment" when you try to run VGL. The work-around is to:
1. Right-click the Protein Investigator icon and choose "Show Package Contents"
2. In the Finder window that appears, open "Contents/Resources"
3. Open the "Java" folder
4. In that, double-click the "Protex.jar" file.
Protein Investigator for Linux/UNIX

(4) A Sample Lab Manual

Lab manual in pdf format.

(5) Source Code

Protein Investigator is Open source and subject to the GNU Public License. The Source Code is available in the format of an Eclipse project file.

This page maintained by Brian White.