Subject: mutant proteins....

From: "Dimitrios Vlachakis" <VlachakisD1[at]Cardiff.ac.uk>
Date: Tue, 28 Sep 2004 22:55:24 +0100

** High Priority **

Dear Holly,

first of all I will asume that you are looking for some freeware. The most user
friendly (in terms of installation and actually using the software is the Deep
View 
Swiss-PdbViewer. It runs for all major platforms (mac 9&10, windows, linux and
iris) and installing it just involves hitting the Ok button a few times. All you
have to do then is to load your protein.pdb file, select the amino acid you want
to mutate and mutate to another on from a list (all with the mouse). 

The software can be found here:                http://www.expasy.org/spdbv/
And a tutorial on protein mutation here:    
http://www.expasy.org/spdbv/text/mutation.htm

A quick comment though: I do not think it is very wise to do mutate amino acids
in a protein using freeware. And there is nothing wrong with freeware, but it is
not up to the job (most of the times). Mutating an amino acid with any piece of
software involves the substitution of the original side chain of the aa with the
one of the new aa. That is quite easy to do and is the easiest part of the whole
mutation job. The problem is how viable and realistic and mutant protein is. The
only way to fix that is to minimise energetically the protein, so that the
energy will drop and the protein will adopt a more stable conformation. Now,
doing that with freeware is simply IMPOSSIBLE! Deep View has implemented a
minimisation algorithm, but it is very poor especailly when dealing with
proteins. It uses the GROMOS 43B1 force field that is only good enough to make
room for new (potentially larger) amino acids. So, it will get stuck in a local
minima as it it will not be able to by pass through high energy barriers. So, i
suggest, that you should either get your hands on a decent software package that
can do both mutating and minimising in a proper scientific way (such as Sybyl,
Moe, hyperchem etc) or if you are going to use freeware to do the mutating part
(such as Deep Blue) find a reliable minimising package. a 30 day evaluation of
hyperchem is available from here: (http://www.hyper.com)

Hope that helps,

Dimitrios Vlachakis                
PhD student in Molecular Modelling 
Medicinal Chemistry Group          
Welsh School of Pharmacy           
Cardiff University                 
                                   
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tel. +44 2920 877221               
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fax. +44 2920 874537               

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