[phenixbb] geometry_minimization makes molprobity score worse
jmholton at lbl.gov
Thu Jul 8 12:49:55 PDT 2021
Thank you Nigel,
Rama-Z "before" (amber energy minimization):
Rama-Z (Ramachandran plot Z-score):
Interpretation: bad |Rama-Z| > 3; suspicious 2 < |Rama-Z| < 3; good
|Rama-Z| < 2.
Scores for whole/helix/sheet/loop are scaled independently;
therefore, the values are not related in a simple manner.
whole: -0.32 (0.86), residues: 62
helix: 0.09 (1.50), residues: 12
sheet: None (None), residues: 0
loop : -0.27 (0.70), residues: 50
whole: -3.20 (0.87), residues: 62
helix: None (None), residues: 0
sheet: -3.03 (1.30), residues: 12
loop : -2.05 (0.72), residues: 50
repeated with cdl=False
whole: -3.35 (0.90), residues: 62
helix: None (None), residues: 0
sheet: -4.51 (1.09), residues: 10
loop : -1.90 (0.75), residues: 52
pdbs and logs are tarballed here:
On 7/8/2021 11:16 AM, Nigel Moriarty wrote:
> This is very interesting from a different perspective but I should
> point out a few things.
> 1. The CDL, which is the default, changes the backbone bonds and
> angles based on phi/psi. Maybe in geometry minimisation this is
> causing the "whirlygig." Can you check with cdl=False?
> 2. In a recent pub
> 1. Sobolev OV, Afonine PV, Moriarty NW, Hekkelman ML, Joosten RP,
> Perrakis A, Adams PD: *A Global Ramachandran Score Identifies
> Protein Structures with Unlikely Stereochemistry.*
> /Structure/ 2020, *28*:1249-1258.e2.
> <http://dx.doi.org/10.1016/j.str.2020.08.005> [PMID: 32857966]
> [PMCID: PMC7642142]
> we argue that percent favoured is not an accurate measure of Rama
> health. Could also provide these numbers?
> Nigel W. Moriarty
> Building 33R0349, Molecular Biophysics and Integrated Bioimaging
> Lawrence Berkeley National Laboratory
> Berkeley, CA 94720-8235
> Phone : 510-486-5709 Email : NWMoriarty at LBL.gov
> Fax : 510-486-5909 Web : CCI.LBL.gov <http://CCI.LBL.gov>
> ORCID : orcid.org/0000-0001-8857-9464
> On Thu, Jul 8, 2021 at 10:28 AM James Holton <jmholton at lbl.gov
> <mailto:jmholton at lbl.gov>> wrote:
> Thank you Pavel for your prompt response!
> I agree with everything you wrote below, and that is a good point
> about 2nd derivatives.
> However, what I'm seeing is the opposite of what you might
> predict. See below.
> On 7/7/2021 11:27 PM, Pavel Afonine wrote:
>> Hi James,
>> thanks for email and sharing your observations!
>>> Greetings all, and I hope this little observation helps improve
>>> things somehow.
>>> I did not expect this result, but there it is. My MolProbity
>>> score goes from 0.7 to 1.9 after a run of
>>> I started with an AMBER-minimized model (based on 1aho), and
>>> that got me my best MolProbity score so far (0.7). But, even
>>> with hydrogens and waters removed the geometry_minimization run
>>> increases the clashscore from 0 to 3.1 and Ramachandran favored
>>> drops from 98% to 88% with one residue reaching the outlier level.
>> It is not a secret that 'standard geometry restraints' used in
>> Phenix and alike (read Refmac, etc) are very simplistic. They are
>> not aware of main chain preferential conformations (Ramachandran
>> plot), favorable side chain rotamer conformations. They don't
>> even have any electrostatic/attraction terms -- only anti-bumping
>> repulsion! Standard geometry restraints won't like any NCI
>> (non-covalent interaction) and likely will make interacting atoms
>> break apart rather than stay close together interacting.
> Yes, there's the rub: I'm not seeing "interacting atoms break
> apart", but rather they are being smashed together. Torsion angles
> are also being twisted out of allowed regions of the Ramachandran
> All this with the x-ray term turned off!
>> With this in mind any high quality (high-resolution) atomic model
>> or the one optimized using sufficiently high-level QM is going to
>> have a more realistic geometry than the result of geometry
>> regularization against very simplistic restraints target. An
>> and previous papers on the topic.
> I agree, but what doesn't make sense to me is how the "simplistic
> restraints" of phenix.geometry_minimization would be so
> inconsistent with the "simplistic restraints" in phenix.molprobity ?
> What I am doing here is starting with an energy-minimized model of
> a 1.0 A structure (1aho). It's not a fancy QM, just the ff14SB
> potential in AMBER. I get my best molprobity scores this way, but
> I need an x-ray refinement program like phenix.refine to compare
> these models with reality. It troubles me that the "geometry" in
> the x-ray refinement program all by itself messes up my molprobity
>>> Just for comparison, with refmac5 in "refi type ideal" mode I
>>> see the MolProbity rise to 1.13, but Clashscore remains zero,
>>> some Ramas go from favored to allowed, but none rise to the
>>> level of outliers.
>> I believe this is because of the nature of minimizer used. Refmac
>> uses 2nd derivative based one, which in a nutshell means it can
>> move the model much less (just a bit in vicinity of a local
>> minimum) than any program that uses gradients only (like Phenix).
> good point.
> So, what should I do to stabilize phenix.geometry_minimization?
> Crank up the non-bonded weight? Restrain to starting coordinates?
>>> Files and logs here:
>>> I suspect this might have something to do with library values
>>> for main-chain bonds and angles? They do seem to vary between
>>> programs. Phenix having the shortest CA-CA distance by up to
>>> 0.08 A. After running thorough minimization on a poly-A peptide
>>> I get:
>>> bond amber refmac phenix shelxl Stryer
>>> C-N 1.330 1.339 1.331 1.325 1.32
>>> N-CA 1.462 1.482 1.455 1.454 1.47
>>> CA-C 1.542 1.534 1.521 1.546 1.53
>>> CA-CA 3.862 3.874 *3.794* 3.854
>>> So, which one is "right" ?
>> I'd say they are all the same, within their 'sigmas' which are
>> from memory about 0.02A:
> I note that 3.874 - 3.794 = 0.08 > 0.02
> This brings me to my pet theory. I think what is going on is
> small errors like this build up a considerable amount of tension
> in the long main chain. For this 64-mer, the contour length of the
> main chain after idealization is ~5 A shorter after
> phenix.geometry_minimization than it is after shelxl or amber.
> That 5 A has to come from somewhere. Without stretching bonds or
> bending angles the only thing left to do is twisting torsions. A
> kind of "whirlygig" effect.
> The question is: is the phenix CA-CA distance too short? Or is
> the amber CA-CA distance too long?
> Shall we vote?
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