FirstGlance/Visualizing Conservation: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
Eric Martz (talk | contribs)
ConfirmAccount, Editor, Print3D, Tester, Bureaucrats, journal, Administrators
30,122 edits
Eric Martz (talk | contribs)
ConfirmAccount, Editor, Print3D, Tester, Bureaucrats, journal, Administrators
30,122 edits
No edit summary
Line 4: Line 4:


<table style="background-color:#ffe0e0"><tr><td>
<table style="background-color:#ffe0e0"><tr><td>
IMPORTANT (January, 2022): Use the unreleased beta-test version [http://bioinformatics.org/firstglance/fgij3.8beta2 FirstGlance 3.8 Beta2] which has many improvements for ConSurf results beyond the publicly available version 3.7. Some of the features shown below are absent in version 3.7.
IMPORTANT (January, 2022): Use the unreleased beta-test version [http://bioinformatics.org/firstglance/fgij3.8beta3 FirstGlance 3.8 Beta3] which has many improvements for ConSurf results beyond the publicly available version 3.7. Some of the features shown below are absent in version 3.7.


Links are provided below to load the example ConSurf results into 3.8beta2.
Links are provided below to load the example ConSurf results into 3.8beta3.


To get your own ConSurf results into 3.8beta2: At your finished ConSurf Job Status page, under the heading ''PDB Files'', right click on ''PDB File with ConSurf Results in its Header, for FirstGlance in Jmol'' and select '''Copy Link Address'''. Then, at [http://bioinformatics.org/firstglance/fgij3.8beta2 FirstGlance 3.8 Beta2], click ''enter a molecule's URL'', paste the address into the slot, and click Submit. (Uploading the downloaded ConSurf PDB file won't work, because the upload mechanism always goes to version 3.7.)
To get your own ConSurf results into 3.8beta3: At your finished ConSurf Job Status page, under the heading ''PDB Files'', right click on ''PDB File with ConSurf Results in its Header, for FirstGlance in Jmol'' and select '''Copy Link Address'''. Then, at [http://bioinformatics.org/firstglance/fgij3.8beta3 FirstGlance 3.8 Beta3], click ''enter a molecule's URL'', paste the address into the slot, and click Submit. (Uploading the downloaded ConSurf PDB file won't work, because the upload mechanism always goes to version 3.7.)
</td></tr></table>
</td></tr></table>


Line 25: Line 25:
Before going further, it is good to decide whether the results are satisfactory, or need optimization. Lets consider [[7bak]], a drug-target protease of SARS-CoV-2 (see [https://pdb101.rcsb.org/motm/242 Coronavirus Proteases]).
Before going further, it is good to decide whether the results are satisfactory, or need optimization. Lets consider [[7bak]], a drug-target protease of SARS-CoV-2 (see [https://pdb101.rcsb.org/motm/242 Coronavirus Proteases]).


:[https://www.bioinformatics.org/firstglance/fgij3.8beta2/fg.htm?mol=7bak_consurf1641000454_pipe.pdb Display 7BAK ConSurf Result in FirstGlance 3.8Beta2]
:[https://www.bioinformatics.org/firstglance/fgij3.8beta3/fg.htm?mol=7bak_consurf1641000454_pipe.pdb Display 7BAK ConSurf Result in FirstGlance 3.8Beta3]


A ConSurf run with all default settings left 10% of the residues with insufficient data<ref name="insufficientdata">When the confidence interval for a conservation value of an amino acid is too large, ConSurf reports "insufficient data" (uncertainty: yellow color). See [https://consurf.tau.ac.il/quick_help.php#RELIABILITY Position Specific Quality] and [https://consurf.tau.ac.il/overview.php#_Toc311131298 Confidence Interval] in the ConSurf documentation.</ref> (yellow color), and the diversity in the multiple sequence alignment (MSA) was too low ([[Interpreting_ConSurf_Results#Average_Pairwise_Distance|average pairwise distance]] 0.34), leaving conservation grades 2 and 3 almost unoccupied. These inadequacies are highlighted by a distribution report displayed by FirstGlance.
A ConSurf run with all default settings left 10% of the residues with insufficient data<ref name="insufficientdata">When the confidence interval for a conservation value of an amino acid is too large, ConSurf reports "insufficient data" (uncertainty: yellow color). See [https://consurf.tau.ac.il/quick_help.php#RELIABILITY Position Specific Quality] and [https://consurf.tau.ac.il/overview.php#_Toc311131298 Confidence Interval] in the ConSurf documentation.</ref> (yellow color), and the diversity in the multiple sequence alignment (MSA) was too low ([[Interpreting_ConSurf_Results#Average_Pairwise_Distance|average pairwise distance]] 0.34), leaving conservation grades 2 and 3 almost unoccupied. These inadequacies are highlighted by a distribution report displayed by FirstGlance.
Line 88: Line 88:
FirstGlance provides an easy and powerful tool to explore residues contacting any specified portion of the model. For this example, we'll use [[acetylcholinesterase]] complexed to the [https://en.wikipedia.org/wiki/VX_(nerve_agent) inhibitor VX], crystal structure [[6cqz]].
FirstGlance provides an easy and powerful tool to explore residues contacting any specified portion of the model. For this example, we'll use [[acetylcholinesterase]] complexed to the [https://en.wikipedia.org/wiki/VX_(nerve_agent) inhibitor VX], crystal structure [[6cqz]].


:[https://www.bioinformatics.org/firstglance/fgij3.8beta2/fg.htm?mol=6cqz_consurf1641072297_pipe.pdb Display 6CQZ ConSurf Result in FirstGlance 3.8Beta2]
:[https://www.bioinformatics.org/firstglance/fgij3.8beta3/fg.htm?mol=6cqz_consurf1641072297_pipe.pdb Display 6CQZ ConSurf Result in FirstGlance 3.8Beta3]


We'll look at the conservation of the residues that contact the ligand/inhibitor VX. From the ''ConSurf View'', go to the FirstGlance Control Panel.  
We'll look at the conservation of the residues that contact the ligand/inhibitor VX. From the ''ConSurf View'', go to the FirstGlance Control Panel.  
Line 176: Line 176:
and Astrid Walrant. ''Crystals'', 2021, '''11'''(9), 1032; [https://doi.org/10.3390/cryst11091032 doi.org/10.3390/cryst11091032].</ref>. Let's see which Trps are conserved in the potassium channel [[1bl8]].
and Astrid Walrant. ''Crystals'', 2021, '''11'''(9), 1032; [https://doi.org/10.3390/cryst11091032 doi.org/10.3390/cryst11091032].</ref>. Let's see which Trps are conserved in the potassium channel [[1bl8]].


:[https://www.bioinformatics.org/firstglance/fgij3.8beta2/fg.htm?mol=1bl8_consurf1640894833_pipe.pdb Display 1BL8 ConSurf Result in FirstGlance 3.8Beta2]
:[https://www.bioinformatics.org/firstglance/fgij3.8beta3/fg.htm?mol=1bl8_consurf1640894833_pipe.pdb Display 1BL8 ConSurf Result in FirstGlance 3.8Beta3]


<table class="wikitable"><tr><td colspan=3><center>
<table class="wikitable"><tr><td colspan=3><center>
Line 249: Line 249:
An example is isopeptide bond-linked chains of ubiquitin. [[7cap]] is an isopeptide-linked trimer of ubiquitin. The carboxy-terminal Gly76 forms an isopeptide bond with Lys48. Here is one ConSurf result (300 sequences in the multiple sequence alignment (MSA), sampled from 10,122 unique similar sequences. The MSA had an [[Interpreting_ConSurf_Results#Average_Pairwise_Distance|average pairwise distance]] of 1.15):
An example is isopeptide bond-linked chains of ubiquitin. [[7cap]] is an isopeptide-linked trimer of ubiquitin. The carboxy-terminal Gly76 forms an isopeptide bond with Lys48. Here is one ConSurf result (300 sequences in the multiple sequence alignment (MSA), sampled from 10,122 unique similar sequences. The MSA had an [[Interpreting_ConSurf_Results#Average_Pairwise_Distance|average pairwise distance]] of 1.15):


:[http://bioinformatics.org/firstglance/fgij3.8beta2/fg.htm?mol=7cap_consurf1639680092_pipe.pdb 7CAP Conservation in FirstGlance 3.8beta2]
:[http://bioinformatics.org/firstglance/fgij3.8beta3/fg.htm?mol=7cap_consurf1639680092_pipe.pdb 7CAP Conservation in FirstGlance 3.8beta3]


First, follow the [[FirstGlance/Evaluating_Protein_Crosslinks#Instructions_for_an_Isopeptide_Bond|instructions for getting a list of the isopeptide crosslinks]].
First, follow the [[FirstGlance/Evaluating_Protein_Crosslinks#Instructions_for_an_Isopeptide_Bond|instructions for getting a list of the isopeptide crosslinks]].
Retrieved from "https://proteopedia.org/FirstGlance/Visualizing_Conservation"