[phenixbb] protein-ligand complex structure

Wei Shi wei.shi118 at gmail.com
Fri Oct 25 09:28:34 PDT 2013


Also, as suggested by Dr Terwilliger, I deleted the ligands and refine only
the protein structure. When I go over the protein structure, I could see
some region didn't fit the density well, so I am thinking of mutating those
regions to alanines and do a refinement in phenix (default settings + NCS
restraints + Secondary structural restraints + Optimize
X-ray/stereochemistry weight +Optimize X-ray/ADP weight), and see whether I
could see better density. Any suggestions or ideas about how to improve the
protein structural model? Thank you so much!

Best,
Wei


On Fri, Oct 25, 2013 at 12:15 PM, Wei Shi <wei.shi118 at gmail.com> wrote:

> Thank you guys for the suggestions!
> For Dr Bosch's question, every monomer binds two ligands, and the first
> binding site is different from the second binding site. The ligand is
> placed differently for the two binding sites for each monomer, but for the
> symmetrical sites in the dimer protein, the ligand is placed in the same
> conformation, even though the density of the ligand in the second monomer
> is not good enough to place the ligand.
> Thank you so much!
>
> Best,
> Wei
>
>
> On Thu, Oct 24, 2013 at 10:31 PM, Bosch, Juergen <jubosch at jhsph.edu>wrote:
>
>> Hi Wei,
>> have you considered modeling two conformations of your ligand in the four
>> sites ?
>> Jürgen
>>
>> On Oct 24, 2013, at 10:19 PM, Wei Shi wrote:
>>
>> Hi all,
>> I am working on a structure of protein-ligand complex. Four ligands are
>> placed for the dimer protein and the density for the two ligands of the
>> first monomer is better than the density for the other two ligands of the
>> second monomer. Ligand is moved to fit density better in Coot (and for two
>> ligands of the first monomer, they fits the density almost perfectly), but
>> after a refinement in phenix (default settings + NCS restraints + Secondary
>> structural restraints + Optimize X-ray/stereochemistry weight +Optimize
>> X-ray/ADP weight), some part of the ligand which fits density good before
>> moved out of the density again...Besides, it always shows green density in
>> Coot for the ligand region even in places where the ligand is in density...
>> Any suggestions or ideas about how to fit the ligand better and why the
>> density for ligands of the second monomer is worse than that for the first
>> monomer and why the ligands would move out of density after refinement?
>> Is it because the protein model is not good enough to get the ligand
>> density good? There is a conformational change upon ligand binding, and I
>> rebuilt some part of the protein manually, and the density for a region of
>> about 30 residues is not very good, and I tried to mutate those to alanies
>> and refine, but it didn't help me see the density better...
>> Any suggestions or ideas on how to improve this protein-complex
>> structural model?  Thank you so much!
>> The statistics for the current best model is as follows, and the
>> resolution of the dataset is 2.8Å.
>>
>>                            start         final
>>   ------------------------------
>> ----------------
>>   R-work:           0.3359        0.2993
>>   R-free:             0.3619        0.3558
>>   RMS(angles):     1.03           1.55
>>   RMS(bonds):    0.006          0.007
>>
>> MolProbity validation
>> Ramachandran outliers:   4.7% (Goal: < 0.2%)
>> Ramachandran favored:  85.3% (Goal: > 98%)
>> Rotamer outliers:   4.5% (Goal: 1%)
>> C-beta outliers:   0    (Goal: 0)
>> Clashscore:   7.43
>> Overall score:   2.56
>>
>> Thank you so much!
>>
>> Best,
>> Wei
>> _______________________________________________
>> phenixbb mailing list
>> phenixbb at phenix-online.org
>> http://phenix-online.org/mailman/listinfo/phenixbb
>>
>>
>>  ......................
>> Jürgen Bosch
>> Johns Hopkins University
>> Bloomberg School of Public Health
>> Department of Biochemistry & Molecular Biology
>> Johns Hopkins Malaria Research Institute
>> 615 North Wolfe Street, W8708
>> Baltimore, MD 21205
>> Office: +1-410-614-4742
>> Lab:      +1-410-614-4894
>> Fax:      +1-410-955-2926
>> http://lupo.jhsph.edu
>>
>>
>>
>>
>>
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>>
>>
>
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