Hi All, I was wondering if there is information/recommendations out there for the resolution required to refine individual anisotropic adps. I think the recommendation for shelx is at least 1.5 A resolution. In addition, is phenix set up and would it make sense to combine tls with individiual anisotropic adps? All comments welcome, Gerwald
Hi Gerwald, from what I recall is if you refine anisotropic ADP at "too low" resolution in other refinement programs, they were often stopping complaining about non-positive definite U or unstable refinement. This seemed to me the main technical limit. In phenix.refine this does not happen but it doesn't mean that refining anisotropic ADP at "too low" resolution will yield meaningful results. I'm not sure that there is an exact resolution borderline for doing (or not doing) individual anisotropic ADP refinement. From my experience, I've never seen a case at ~1.5A and higher where switching from iso- to anisotropic model was not good. Then this question transforms into "at which resolution you start refining waters as anisotropic?"... A very rough number I would say is 1.2-1.1A and higher. In-between 1.5 and 1.7 (1.8A) is a "gray zone", where it is very likely that anisotropic ADP refinement will result in over-fitting, however there is a chance that it might still be valid. Summarizing, if I have a data at resolution between between 1.5 and 1.8A resolution, I just try two refinements: in one refining isotropic and in another refining anisotropic ADPs. Rfree is your best friend here (and Rfree-Rwork). In my opinion, this is the most robust and cheep way to get the answer. Cheers, Pavel. On 12/11/2008 7:48 AM, gerwald jogl wrote:
Hi All,
I was wondering if there is information/recommendations out there for the resolution required to refine individual anisotropic adps. I think the recommendation for shelx is at least 1.5 A resolution. In addition, is phenix set up and would it make sense to combine tls with individiual anisotropic adps?
All comments welcome, Gerwald _______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
Question at large: do any formalisms exist, or are any envisioned, that deal with this question more rigorously? E.g. in principle everything is always ADP, but as resolution decreases, the restraints are tightened accordingly, so that there is an appropriately refined continuum from fully ADP @ 1A to isotropic @ 2A to TLS only @ 3A? I know for a fact I've heard about this somewhere, but can't remember where. phx. that in principle always refine ADP for everything, but tighten the restraints automatically, Pavel Afonine wrote:
Hi Gerwald,
from what I recall is if you refine anisotropic ADP at "too low" resolution in other refinement programs, they were often stopping complaining about non-positive definite U or unstable refinement. This seemed to me the main technical limit.
In phenix.refine this does not happen but it doesn't mean that refining anisotropic ADP at "too low" resolution will yield meaningful results.
I'm not sure that there is an exact resolution borderline for doing (or not doing) individual anisotropic ADP refinement. From my experience, I've never seen a case at ~1.5A and higher where switching from iso- to anisotropic model was not good. Then this question transforms into "at which resolution you start refining waters as anisotropic?"... A very rough number I would say is 1.2-1.1A and higher.
In-between 1.5 and 1.7 (1.8A) is a "gray zone", where it is very likely that anisotropic ADP refinement will result in over-fitting, however there is a chance that it might still be valid.
Summarizing, if I have a data at resolution between between 1.5 and 1.8A resolution, I just try two refinements: in one refining isotropic and in another refining anisotropic ADPs. Rfree is your best friend here (and Rfree-Rwork). In my opinion, this is the most robust and cheep way to get the answer.
Cheers, Pavel.
On 12/11/2008 7:48 AM, gerwald jogl wrote:
Hi All,
I was wondering if there is information/recommendations out there for the resolution required to refine individual anisotropic adps. I think the recommendation for shelx is at least 1.5 A resolution. In addition, is phenix set up and would it make sense to combine tls with individiual anisotropic adps?
All comments welcome, Gerwald _______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
_______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
Hi Frank, - I tend to call it "isotropic atomic displacement parameters" and "anisotropic atomic displacement parameters", correspondingly "isotropic ADP" and "anisotropic ADP", which is also consistent with: J. Appl. Cryst. (2002). 35, 477-480 On the handling of atomic anisotropic displacement parameters R. W. Grosse-Kunstleve and P. D. Adams - What you wrote below can be boiled down to the question: "Are very tight restraints equivalent to constraints?". A few years ago I tried to see if refinement of individual coordinates with very tight restraints can approach rigid body refinement. The answer I got was "no". Of course one needs to keep in mind that it might all be dependent on particular implementation, minimizers, and other technicalities. I don't know what mathematics says here. - I would just take whole PDB and re-refine it alternative options at appropriate resolutions (for example, use iso- or anisotropic ADP for model at resolution between 1.2 and 2.0A) and see how the best choice correlates with model/data characteristics. I'm sure there will be dependencies allowing you to get some empirical rules. However, I'm sure there will be a number of exceptions, where only trying appropriate options will bring you the definitive answer. - Using TLS is another branch of this story. The total atomic B-factors can be presented at least as a sum of three contributions: Utotal = Ulocal + Utls + Ucryst where - Utotal is the total ADP, - Ulocal reflects the local atomic vibration (also named as residual B) and should obey Hirshfeld's rigid bond criteria (F.L. Hirshfeld. Acta Cryst. (1976). A32, 239-244. "Can X-ray data distinguish bonding effects from vibrational smearing?"); - Ucryst reflects global lattice vibrations (Ucryst is determined and refined at anisotropic scaling), - Utls reflects global motion (which can be further subdivided into the motion of the molecule as a whole and into the motion of its domains). Obviously, the presence of global motion is not the function of data resolution (in sense that a molecule does not "know" about your crystallographic experiment and its resolution), so ideally you need always model it (= you need always use TLS). However this faces a number of technical problems currently making it impossible: - robust and reliable choice of TLS groups; - robust and reliable separation of Utls and *anisotropic* Ulocal. A first attempt is described here: P. Afonine & A. Urzhumtsev. (2007). CCP4 Newsletter on Protein Crystallography. 45. Contribution 6. "On determination of T matrix in TLS modeling"; - not to mention a strong correlations of parameters which potentially may lead to troubles in optimization flow; - ... and many other... Phenix.refine has a pretty sophisticated algorithm of combined TLS refinement which is outlined at slides #28-32: http://cci.lbl.gov/~afonine/aca2008_knoxville_neutron/ Pavel. On 12/11/2008 9:08 AM, Frank von Delft wrote:
Question at large: do any formalisms exist, or are any envisioned, that deal with this question more rigorously? E.g. in principle everything is always ADP, but as resolution decreases, the restraints are tightened accordingly, so that there is an appropriately refined continuum from fully ADP @ 1A to isotropic @ 2A to TLS only @ 3A?
I know for a fact I've heard about this somewhere, but can't remember where.
phx.
that in principle always refine ADP for everything, but tighten the restraints automatically,
Pavel Afonine wrote:
Hi Gerwald,
from what I recall is if you refine anisotropic ADP at "too low" resolution in other refinement programs, they were often stopping complaining about non-positive definite U or unstable refinement. This seemed to me the main technical limit.
In phenix.refine this does not happen but it doesn't mean that refining anisotropic ADP at "too low" resolution will yield meaningful results.
I'm not sure that there is an exact resolution borderline for doing (or not doing) individual anisotropic ADP refinement. From my experience, I've never seen a case at ~1.5A and higher where switching from iso- to anisotropic model was not good. Then this question transforms into "at which resolution you start refining waters as anisotropic?"... A very rough number I would say is 1.2-1.1A and higher.
In-between 1.5 and 1.7 (1.8A) is a "gray zone", where it is very likely that anisotropic ADP refinement will result in over-fitting, however there is a chance that it might still be valid.
Summarizing, if I have a data at resolution between between 1.5 and 1.8A resolution, I just try two refinements: in one refining isotropic and in another refining anisotropic ADPs. Rfree is your best friend here (and Rfree-Rwork). In my opinion, this is the most robust and cheep way to get the answer.
Cheers, Pavel.
On 12/11/2008 7:48 AM, gerwald jogl wrote:
Hi All,
I was wondering if there is information/recommendations out there for the resolution required to refine individual anisotropic adps. I think the recommendation for shelx is at least 1.5 A resolution. In addition, is phenix set up and would it make sense to combine tls with individiual anisotropic adps?
All comments welcome, Gerwald _______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
_______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
_______________________________________________ phenixbb mailing list [email protected] http://www.phenix-online.org/mailman/listinfo/phenixbb
participants (4)
-
Frank von Delft -
gerwald jogl -
Pavel Afonine -
Pavel Afonine