Subject: mutant proteins

From: Oliver Hucke <ohucke(at)u.washington.edu>
Date: Wed, 29 Sep 2004 10:34:01 -0700

Holly,

another free program that can be used for mutating single residues is 
MODELLER (http://salilab.org/modeller/modeller.html). This is a full 
homology modeling program suite. The standard optimizing protocol 
employs simulated annealing which avoids the "local minimum problem" 
that Dimitrios pointed out. And the output is a proper pdb file - no 
scripting required. It takes a little while to learn the program though.

Best regards,
Oliver

-- 
________________________________________________________________

Oliver Hucke, Dr.
Biomolecular Structure Center   Health Sciences Building - K418C
Dept. of Biochemistry           1959 NE Pacific St.
University of Washington        phone: (206) 685 7046
Box 357742                      fax  : (206) 685 7002
Seattle, WA 98195-7742          email: ohucke(at)u.washington.edu
________________________________________________________________

A free minimizer for proteins is TINKER from the Jay Ponder group at 
WashU.  It has among others an AMBER FF (or should I say a Kollman FF?) 
  implementation, with several of the published parameter sets.  Beware: 
   The translation from the working TINKER xyz format back to a fully 
informative pdb format can be painful if you have limited scripting  skills.

Steve Bowlus

On Sep 28, 2004, at 2:55 PM, Dimitrios Vlachakis wrote:

** 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

Redwood Building
King Edward VII Avenue
CF10 3XF
Cardiff
Wales, UK

tel. +44 2920 877221
tel. +44 2920 874551 (lab)
fax. +44 2920 874537

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