Introduction

The Multiple Sequence Alignment extension to VMD

The Multiple Sequence Alignment (Multiseq) extension to VMD links protein structures to protein sequences and allows you to compare proteins in terms of structure and sequence.

Multiseq is designed to study protein mechanism through available genetic information, such as evolutionary conservation, offering biomedical researchers a new tool to examine protein structure and function.

This tutorial can be used by both new and previous users of VMD. However, it is recommended that new users go through the ``VMD Molecular Graphics'' tutorial, in order to gain further knowledge about the overall program.¹

The present tutorial has been designed specifically for VMD with Multiseq and should take about an hour to complete in its entirety.

Aquaporins

We will use the family of aquaporins for a case study in the applications of the Multiple Sequence Alignment tool. Aquaporins (AQPs) are membrane channel proteins found in a wide range of organisms, from archaea and bacteria to plants and animals. AQPs facilitate the rapid transport of water across cellular membranes and are of fundamental importance to the control of cell volume and transcellular water traffic.
In humans, there are at least 11 different aquaporin types (see cover). The kidney alone contains AQP1, AQP2 and AQP3. These proteins are responsible for filtering hundreds of liter of water per day in the human body. In addition to water, a subfamily of AQPs, named aquaglyceroporins, also selectively transport small molecules such as glycerol.

Here we use Multiseq to conduct a comparative study of the structure and sequence of four aquaporins from different species: human AQP1, bovine AQP1, AqpZ from E.coli, and GlpF (E.coli glycerol facilitator). The aquaporin AqpM from Archaea will be introduced in the last section.

Getting Started

Multiseq, in its current release, is operable on the following platforms:

• Macintosh OS X
• Solaris
• Linux
• Windows

This tutorial requires certain files, located in
 
/Desktop/Workshop/aqp-tutorial/aqp-tutorial-files/
 
The file structure of this directory appears in the following figure:

Needed Software

VMD, containing the MultiSeq plugin (version of VMD 1.8.7 beta 6 and later), can be obtained from http://www.ks.uiuc.edu/Research/vmd. Once VMD is installed, you can start the tutorial by starting VMD. To start VMD:

• Mac OS X: Double click on the VMD application icon in the Applications directory.
• Linux and SUN: Type vmd in a terminal window.
• Windows: Select Start $\rightarrow$ Programs $\rightarrow$ VMD.

Getting Help

We have set up a mailing list, Tutorials-L, which will act as a forum for discussions and questions about the tutorials offered by the Theoretical and Computational Biophysics Group (http://www.ks.uiuc.edu/Training/Tutorials/). If you have questions, comments, etc, please suscribe to the list. Instructions can be found at http://www.ks.uiuc.edu/Training/Tutorials/mailing_list.