Subject: Summary: modelling protein under point mutation

From: Jeremy R Greenwood <[email-masked]>
Date: Thu, 23 Feb 1995 14:11:03 +1100 (EST)

Thanks to all who responded to my request for information about
protein structure determination under point mutation. There are some
excellent suggestions.

Jeremy

Original request:
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Greetings to all,

I have just been approached with a project concerning the modelling of
the changes in structure and function of a protein under various
point mutations. The X-ray crystal structure is known, as are all the 
different inherited single point mutations which lead to a particular 
pathology. Not being a protein modeller by trade, I'm asking for some 
preliminary qualitative advice:

* Roughly how hard is it to model changes in structure or binding 
resulting from a single point mutation? (apparantly many such typical
mutations are from charged to uncharged residues). Is it feasible to 
obtain meaningful results, given the state of the art? (obviously this 
will depend on the given system, but perhaps some out there have 
attempted this kind of problem previously.)

* What kinds of tools are necessary or useful? (e.g. AMBER, MD, MC, 
simulated annealing, semi-empirical calculations on local regions with 
substrate binding, etc.) Which software packages are recommended
(anything cheaper than Biosym?) and what level of hardware?

* Any other advice for the neophyte protein modeller? Recommended
texts?

Summary to follow, as per usual.

Naively,
	Jeremy
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