-Just to make a note, there has actually been some discussion in the
published literature recently (ok maybe past ten years) about what
terms; simply steric (as originally) or hydrogen bonding etc
might be needed to explain observed backbone angular values.
Tommi
On Sep 26, 2011, at 5:44 PM, Dirk Kostrewa wrote:
> Dear Nat,
>
> yes, I fully agree - all these restraints that improve the geometry
> either by restraining to high-resolution structures or by
> introducing H-bond restraints for secondary structures are very
> useful for low-resolution structures!
>
> I see your argument with the Ramachandran plot. But imagine a set of
> very strong non-bonding/bonding restraints that would result in an
> absolutely clean Ramachandran plot for any structure, then the
> Ramachandran plot would become useless even in the absence of any
> phi/psi-restraints. So, I prefer to err a bit on the safe side here
> by saying "not a truly independent measure".
>
> Personally, I think, that ALL refinement programs, including the
> real-space refinement in Coot, would benefit from inclusion of
> proper H-bonding terms (something, that for instance the very old X-
> Plor version did), since this would automatically restrain secondary
> structures and other hydrophilic interactions to some reasonable
> geometry, even at very low resolution.
>
> Best regards,
>
> Dirk.
>
> Am 26.09.11 16:17, schrieb Nat Echols:
>>
>> On Mon, Sep 26, 2011 at 1:53 AM, Dirk Kostrewa <[log in to unmask]
>> > wrote:
>> when I played with H-bond restraints for secondary structures for
>> the refinement of a 4.3 A structure (only a few weeks before they
>> were introduced in phenix), I've made the following observation: at
>> low resolution without H-bond restraints for secondary structures,
>> the carbonyl groups of these secondary structures take the liberty
>> within their globbish electron densities to deviate from their
>> ideal H-bond conformation, resulting in a tight "belt" of outliers
>> around the preferred Ramachandran regions, with typical deviations
>> of only a few degrees. Introducing the additional H-bond restraints
>> for maintaining secondary structures pulls these outlier carbonyl
>> groups back into the preferred Ramachandran regions. In my case,
>> the number of Ramachandran outliers was reduced to less than one
>> half! Although, these H-bond restraints do not directly include
>> information about allowed Ramachandran regions, the Ramachandran
>> plot is actually affected by these restraints. Thus, at least in my
>> opinion, the Ramachandran plot is then not a truly independent
>> measure for model quality, anymore. The same holds true for all
>> geometrical restraints, of course.
>>
>> It depends on how strictly you assess the "independence" of
>> validation criteria. The Ramachandran plot is considered valid in
>> most cases because refinement programs traditionally do not
>> restrain phi and psi angles, so we need to rely on the accuracy of
>> the data (and our placement of atoms) and various complementary
>> geometry restraints (especially nonbonded) to keep residues in the
>> favorable regions of the plot. There are a variety of ways to make
>> the plot better by modification of the model and/or restraints
>> (adding hydrogens, increasing the weight on the nonbonded
>> restraints, secondary structure restraints, etc.), none of which
>> are as drastic as directly restraining the model to the plot. I
>> don't really view this as biasing the plot, for two reasons: a) the
>> quantity being measured is independent of the quantity restrained,
>> and b) at least in my hands, these modifications never completely
>> fix the problem of Ramachandran outliers. (It's the loop regions
>> that are really awful.)
>>
>> Anyway, I don't think anyone should feel bad about using this kind
>> of restraint at low resolution. The caveat is that of all the
>> specialized restraints that we (Jeff Headd and I) have been testing
>> for low-resolution refinement (in Phenix), nothing works nearly as
>> well in preserving good geometry, and usually improving the R-
>> factors, as restraining model parameters to a related high-
>> resolution structure, when one is available. Fortunately, every
>> modern refinement program has this ability in some form, and I
>> expect that this is going to have the most impact in improving the
>> overall quality of low-resolution structures.
>>
>> -Nat
>
> --
>
> *******************************************************
> Dirk Kostrewa
> Gene Center Munich, A5.07
> Department of Biochemistry
> Ludwig-Maximilians-Universität München
> Feodor-Lynen-Str. 25
> D-81377 Munich
> Germany
> Phone: +49-89-2180-76845
> Fax: +49-89-2180-76999
> E-mail: [log in to unmask]
> WWW: www.genzentrum.lmu.de
> *******************************************************
Tommi Kajander, Ph.D.
Structural Biology and Biophysics
Institute of Biotechnology
University of Helsinki
Viikinkaari 1
(P.O. Box 65)
00014 Helsinki
Finland
p. +358-9-19158903
[log in to unmask]
|