And, to add a serious and a not-so-serious comment:
(serious) What we're doing is determining a crystal structure - not a protein structure. Success is to model, as well as possible, what is in the crystal, and that includes protein, ligand, water, ions, and whatever else is in there. A successful crystal structure determination may or may not have "biological significance". It's nice if it does, and it makes it easier to publish the structure. While we embark upon projects intending provide new insight into enzyme mechanisms or other problems, not all crystal structures do that.
(perhaps not so serious) Biological significance depends as much on the intuition (if the investigator gets it right) and imagination (if they get it wrong) of the investigators as it does on the resolution or completeness of the model. There are a lot well presented stories accompanying crystal structures (and other types of experiments) in the literature. Some are not at all chemically feasible.
Sue
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>> -----Original Message-----
>> From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of
>> Ed Pozharski
>> Sent: Thursday, December 13, 2012 20:01
>> To: [log in to unmask]
>> Subject: Re: [ccp4bb] refining against weak data and Table I stats
>>
>> On Thu, 2012-12-13 at 17:50 +0000, Theresa Hsu wrote:
>>> Being a beginner crystallographer, may I ask a basic question? On how
>>> many occasions does it make a *biological* difference between having a
>>> structure at 1.42 and 1.6 A?
>>
>> And your definition of "biological difference" is exactly what? Every field of
>> experimental science strives to obtain results of best possible quality, why
>> should macromolecular crystallography be different? Would you be satisfied
>> with a report that "binding assays show presence of binding which perhaps is
>> in submicromolar range but we don't care to determine actual binding
>> constants"?
>>
>> You should also realize that while ccp4bb has evolved over years into a forum
>> covering topics well beyond computational aspects of macromolecular
>> crystallography, at its core it still is made of individuals who value method
>> development. As Black Queen told Alice - it takes all the running you can do
>> to keep in the same place.
>>
>>> I think this question also extends to adding in water molecules just
>>> to make statistics look good.
>>
>> I never understood this attitude. Compared to O/CNS combination on SGIs
>> (which are all excellent products) refining a model using COOT/REFMAC on a
>> modern Core i7 machine is a cakewalk. Let's see - one spends from several
>> months to a year or two going from gene to diffraction data, and spending a
>> week carefully rebuilding in order to obtain the best most complete model
>> possible is undue burden? I am not a perfectionist by any measure, but
>> deliberately not placing water molecules that you can place because it "does
>> not make biological difference" can hardly be justified.
>>
>> Cheers,
>>
>> Ed.
>>>
>>
>> --
>> Oh, suddenly throwing a giraffe into a volcano to make water is crazy?
>> Julian, King of Lemurs
Dr. Sue A. Roberts
Dept. of Chemistry and Biochemistry
University of Arizona
1041 E. Lowell St., Tucson, AZ 85721
Phone: 520 621 8171 or 520 621 4168
[log in to unmask]
http://www.cbc.arizona.edu/xray or
http://www.cbc.arizona.edu/facilities/x-ray_diffraction
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