User:Eric Martz/Sandbox 3

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==ConSurf Prototype==
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==Notes on mini- and microproteins==
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{{STRUCTURE_2hhd| PDB=2hhd | SCENE= }}
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===Micro===
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===Scenes===
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*2018: Microproteins are "translated from protein-coding small open reading frames (smORFs, less than 100–150 codons in length)." "to reduce false positives... most genome annotation pipelines required ORFs to be at least 300 nucleotides long (i.e. 100 amino acids) resulting in most smORFs being missed." <ref>PMID: 30415582</ref>
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Opening the proposed <i>Evolutionary Conservation</i> section below the molecule would automatically color all chains by ConSurf, and spacefill them. Checkboxes in this section, one per chain, would be checked when the section is first opened. Unchecking a given chain would render it as a gray backbone (as in ConSurf). Ligands will be ball and stick, with dot surfaces, colored by element (as in ConSurf; oops, forgot to do the sulfates in some scenes). Here, for demonstration purposes, are 5 of the 16 possible scenes that 4-chain-checkboxes could generate:
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*<scene name='User:Eric_Martz/Sandbox_3/Consurf/1'>ConSurf color all 4 chains</scene> (2 alphas, A and C, and 2 betas, B and D, in 2HHD).
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*<scene name='User:Eric_Martz/Sandbox_3/Consurf/2'>ConSurf color only chains A and B</scene> (one alpha, one beta)
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*<scene name='User:Eric_Martz/Sandbox_3/Consurf/3'>ConSurf color only chains A and C</scene> (both alphas)
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*<scene name='User:Eric_Martz/Sandbox_3/Consurf/4'>ConSurf color only chain A</scene>
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*<scene name='User:Eric_Martz/Sandbox_3/Consurf/5'>All chains unchecked</scene>
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===Button Tests===
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*2015: "MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect." They "disrupt the formation of homodimeric, heterodimeric, or multimeric complexes". "The term ‘microProtein’ was coined due to their small size and negative regulatory similarity to miRNAs" <ref>PMID: 26115780</ref>
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<!-- UNNECESSARY WITH REVISED IF LOGIC
 
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<jmol>
 
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<jmolButton>
 
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<script> ~A = 1;~B = 1;</script>
 
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<text>set A, B</text>
 
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</jmolButton>
 
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</jmol>
 
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-->
 
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<jmol>
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*2011 review <ref>PMID: 21151039</ref>
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<jmolButton>
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<script>if (consurf_A!=0); select:A; spacefill off;color translucent -1; consurf_A = 0;javascript "document.getElementById('jmb_A').value='A [ ]'"; else; select:A; spacefill on; color opaque;consurf_A = 1;javascript "document.getElementById('jmb_A').value='A [x]';"; endif;</script>
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<text>A [ ]</text>
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<name>jmb_A</name>
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</jmolButton>
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</jmol> Lower case x so it doesn't look like chain X. Two spaces in empty [ ]. Uses document.getElementById('jmb_A').value='...'. Works in
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*Internet Explorer 7/Windows XP
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===Mini===
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*Internet Explorer 6/Windows 98
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*Firefox2/Windows 98/Windows XP
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*Firefox2/OSX
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*Safari/OSX (mouse movement needed to get the text change, else button label is always one step behind).
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<!--
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*2017: Miniproteins are "polypeptide chains <40 amino acids in length that adopt defined and stable 3D structures". They are often designed, or screened from designed libraries. <ref>PMID: 28832117</ref>
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Checkmark is &#10003;
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<jmol>
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<jmolButton>
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<script>if (~B==1); select:B; spacefill off;color translucent -1; ~B = 0;javascript "bB.value='B[ ]'"; else; select:B; spacefill on; color opaque;~B = 1;javascript "bB.value='B[x]'"; endif;</script>
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<text>\B\[✓\]</text>
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<name>bB</name>
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</jmolButton>
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</jmol> The checkmark causes the previous characters to disappear. ??
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-->
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<jmol>
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*2017: De novo designed: <ref>PMID: 28953867</ref>
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<jmolButton>
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<script>if (~B!=0); select:B; spacefill off;color translucent -1; ~B = 0;javascript "bB.value='B [ ]'"; else; select:B; spacefill on; color opaque;~B = 1;javascript "bB.value='B [x]'"; endif;</script>
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<text>B [ ]</text>
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<name>bB</name>
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</jmolButton>
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</jmol> Uses bB.value='...'. Firefox: javascript error, bB is not defined, so no button text change in Firefox. Firefox every second click ignored unless mouseout between clicks. Works in Safari/OSX and Internet Explorer 6/7/Windows.
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Checkmark: &#10003; but if it is used in the button text label, the previous characters don't appear. Could maybe use a button label &#10003;A instead of A[&#10003;], but haven't tested it. And in Internet Explorer 7, this "checkmark" appears as two horizontal bars. Not worth pursuing, I think. (Similarly, I often see problems with greek letters, so it is better to spell them out in English than to try to show the actual greek letter.)
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*2015: Viruses have hydrophobic, membrane-spanning miniproteins. <ref>PMID: 26057606</ref> <ref>PMID: 24742054</ref>
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===User Interface & Color Key===
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*2011: Cysteine knot miniproteins are a subset of miniproteins that can be natural or engineered. <ref>PMID: 22204431</ref>
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To keep the user interface simple in Proteopedia, at least to start with, I propose that the only controls will be one checkbox per chain to ConSurf-color+spacefill each chain or not. The color key will not be interactive (unlike in ConSurf). Clicking the link <i>Complete results at ConSurf</i> will provide a path to the display in <i>FirstGlance in Jmol</i> with many more options.
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==In Proteopedia==
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*There are about 60 entries found with a search for "miniprotein" (but no such category).
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*[[:Category:Microprotein]] has 3 entries, and [[:Category:Hybrid microprotein]] has 1.
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Below are non-interactive mockups just to suggest the look for a user interface that would be an additional expandable block beneath the molecule.
 
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*Links do not work.
 
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*When a chain is "checked" [x], it will be colored by conservation, and spacefill it. When unchecked, that chain will become a gray backbone trace.
 
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*The link to ''Explanation'' would go to a Proteopedia page of explanation. It might be a revised version of [[Conservation, Evolutionary]].
 
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==References==
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<b>Before expanding this section, it could look like this:</b>
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<references />
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<table border="0" cellspacing="0" cellpadding="2" width="330">
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<tr>
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<td align="left" colspan="2" bgcolor="#bac9f7">
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<font color="#2020e0"><b>Evolutionary Conservation:</b></font>
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp;
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[<font color="#1010ff">show</font>]
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</td></tr>
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</table>
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<br>
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<b>After expanding, it could look like this (using buttons):</b>
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<table class="collapsible collapsed" border="0" cellspacing="0" width="330">
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<tr>
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<td align="left" colspan="2" bgcolor="#bac9f7">
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<font color="#2020e0"><b>Evolutionary Conservation:</b></font>
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp; &nbsp;
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[<font color="#1010ff">hide</font>]
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</td></tr>
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<tr><td colspan="2" style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;"></td></tr>
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<!-- <tr><td colspan='2' style="background-color:#bac9f7;"> -->
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<tr><td colspan='2' style="background-color:#bac9f7;">
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[[Image:Consurf_key_small.gif|center]]
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</td></tr>
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<tr><td style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;">
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<b>Toggle Conservation Colors:</b>
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</td><td align="left" style="background-color:#ace3ac;border-top:2px solid #dddddd; border-right:2px solid #dddddd" width="230">&nbsp;Rows = identical sequences:<br>
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<jmol>
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<jmolButton>
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<script>if (consurf_A!=0); select:A; spacefill off;color translucent -1; consurf_A = 0;javascript "document.getElementById('jmb_AA').value='A [ ]'"; else; select:A; spacefill on; color opaque;consurf_A = 1;javascript "document.getElementById('jmb_AA').value='A [x]';"; endif;</script>
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<text>A [ ]</text>
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<name>jmb_AA</name>
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</jmolButton>
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</jmol>
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<jmol>
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<jmolButton>
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<script>if (consurf_C!=0); select:C; spacefill off;color translucent -1; consurf_C = 0;javascript "document.getElementById('jmb_C').value='C [ ]'"; else; select:C; spacefill on; color opaque;consurf_C = 1;javascript "document.getElementById('jmb_C').value='C [x]';"; endif;</script>
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<text>C [ ]</text>
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<name>jmb_C</name>
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</jmolButton>
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</jmol>
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<hr noshade>
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<jmol>
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<jmolButton>
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<script>javascript "alert('Not implemented in mockup.')"</script>
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<text>B [ ]</text>
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<name>jmb_BB</name>
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</jmolButton>
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</jmol>
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<jmol>
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<jmolButton>
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<script>javascript "alert('Not implemented in mockup.')"</script>
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<text>D [ ]</text>
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<name>jmb_D</name>
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</jmolButton>
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</jmol>
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</td></tr>
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<tr><td style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;"> <b>Further Information:</b>
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</td><td align="left" style="background-color:#ace3ac;border-top:2px solid #dddddd; border-right:2px solid #dddddd" width="230">
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<font color="#2020e0">Explanation
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<br><br>
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Complete results at ConSurf</font>
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</td></tr>
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</table>
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<!--
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<br>
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<b>After expanding, it could look like this (using green links):</b>
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<table class="collapsible collapsed" border="0" cellspacing="0" width="330">
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<tr>
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<td align="left" colspan="2" bgcolor="#bac9f7">
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<font color="#2020e0"><b>Evolutionary Conservation:</b></font>
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp; &nbsp; &nbsp;
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&nbsp; &nbsp; &nbsp;
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[<font color="#1010ff">hide</font>]
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</td></tr>
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<tr><td colspan="2" style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;"></td></tr>
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<tr><td colspan='2' style="background-color:#bac9f7;">
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[[Image:Consurf_key_small.gif|center]]
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</td></tr>
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<tr><td style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;">
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&nbsp;</td><td align="left" style="background-color:#ace3ac;border-top:2px solid #dddddd; border-right:2px solid #dddddd" width="230">
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<font color="#009000"><b>Hide all conservation colors.</b></font>
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</td></tr><tr><td style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;">
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<b>Click Chain(s) to Show Conservation:</b>
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</td><td align="left" style="background-color:#ace3ac;border-top:2px solid #dddddd; border-right:2px solid #dddddd" width="230">&nbsp;Rows = identical sequences:<br>
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<font color="#009000"><b>A C<br>B D</b></font>
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</td></tr>
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<tr><td style="background-color:#bac9f7;color:#040d44;vertical-align:top;text-align:left;"> <b>Further Information:</b>
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</td><td align="left" style="background-color:#ace3ac;border-top:2px solid #dddddd; border-right:2px solid #dddddd" width="230">
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<font color="#2020e0">Explanation
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<br><br>
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Complete results at ConSurf</font>
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</td></tr>
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</table>
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-->
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===Scripts===
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When the <i>Evolutionary Conservation</i> block is expanded, a master script is run that colors and spacefills all chains.
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<!--
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Importantly, it also defines 10 groups of residues, to be colored as <i>insufficient data</i> (~con10), and grades 1-9 (conserved - variable, ~con1, ~con2, ..., ~con9). These terms greatly simplify the script needed when a checkbox is changed.
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-->
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The scripts below will need to be tweaked a bit for [[NMR Ensembles of Models]]. In these, we will want to show only model 1 for ConSurf scenes.
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====Changing a Checkbox====
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After a checkbox is changed, the currently checked chains are put into this script:
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<tt><pre>select protein
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spacefill off
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select (:a,:c) # LIST OF CHECKED CHAINS
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spacefill
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</pre></tt>
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The gray backbones for all chains are always rendered, but are hidden within spacefilled atoms, when a chain is spacefilled. Once set, the colors never change. Although the backbones are gray, the atoms are ConSurf-colored. All a checkbox needs to do is spacefill the appropriate set of chains. The colors remain.
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====Master ConSurf Script====
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The master script will need to be generated by ConSurf for each PDB code. It differs in a few minor ways from the per-chain scripts currently being generated.
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# All chains are colored and spacefilled, not just one chain. This includes both sequence-identical chains, and sequence different chains.
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# The 10 color grade groups of residues are selected only once, for all chains, as shown in the example script below.
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# The defined Jmol variables ~con1, ~con2, ... ~con10 now each begin with a tilde (~). This is the recommended practice for such variables in Jmol, to avoid possible conflicts.
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<b>MASTER SCRIPT</b>
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<tt><pre>
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script "/wiki/scripts/allRenderingsOff.spt"
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select hetero and not water
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spacefill 0.5
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wireframe 0.3
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color cpk
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dots
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script 2hhd_consurf.spt # from pre-calculated ConSurf dataset, one per PDB code
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select protein
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define ~consurf_to_color selected
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script consurf_color_levels.spt
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select protein
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spacefill
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backbone 0.4
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color backbone [xc8c8c8]
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select nucleic
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cartoon
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color cpk
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</pre></tt>
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<b>consurf_color_levels.spt</b>
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<br>
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The purpose of this script is to color all protein atoms according to ConSurf. This script can be "constant", the same for all PDB entries. A big advantage of this script is that it sets the ConSurf color values. If any ever need to be changed, only this one script needs changing. This script requires that the atom subset term <b>~consurf_to_color</b> be defined beforehand.
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<tt><pre>
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#any protein not in a consurf level, e.g. short peptides not processed by consurf, is colored here
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select ~consurf_to_color
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color yellow
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#each consurf level is now colored with the standard consurf colors
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select ~consurf_to_color and ~con10
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color [255,255,150]
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select ~consurf_to_color and ~con9
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color [160,37,96]
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select ~consurf_to_color and ~con8
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color [240,125,171]
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select ~consurf_to_color and ~con7
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color [250,201,222]
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select ~consurf_to_color and ~con6
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color [252,237,244]
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select ~consurf_to_color and ~con5
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color [255,255,255]]
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select ~consurf_to_color and ~con4
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color [255,255,150]
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select ~consurf_to_color and ~con3
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color [255,255,150]
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select ~consurf_to_color and ~con2
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color [255,255,150]
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select ~consurf_to_color and ~con1
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color [255,255,150]
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</pre></tt>
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<b>2hhd_consurf.spt</b>
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<br>
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The purpose of this script is to define ~con1, ~con2, ... ~con10, the atoms in each consurf level. This script does not color or spacefill the atoms. The amino acids per color grade are combined into each ~con## term for all chains as shown in the example script below.
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<tt><pre>
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</pre></tt>
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Current revision

Contents

Notes on mini- and microproteins

Micro

  • 2018: Microproteins are "translated from protein-coding small open reading frames (smORFs, less than 100–150 codons in length)." "to reduce false positives... most genome annotation pipelines required ORFs to be at least 300 nucleotides long (i.e. 100 amino acids) resulting in most smORFs being missed." [1]
  • 2015: "MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect." They "disrupt the formation of homodimeric, heterodimeric, or multimeric complexes". "The term ‘microProtein’ was coined due to their small size and negative regulatory similarity to miRNAs" [2]


  • 2011 review [3]

Mini

  • 2017: Miniproteins are "polypeptide chains <40 amino acids in length that adopt defined and stable 3D structures". They are often designed, or screened from designed libraries. [4]
  • 2017: De novo designed: [5]
  • 2015: Viruses have hydrophobic, membrane-spanning miniproteins. [6] [7]
  • 2011: Cysteine knot miniproteins are a subset of miniproteins that can be natural or engineered. [8]

In Proteopedia


References

  1. ↑ Rathore A, Martinez TF, Chu Q, Saghatelian A. Small, but mighty? Searching for human microproteins and their potential for understanding health and disease. Expert Rev Proteomics. 2018 Dec;15(12):963-965. doi:, 10.1080/14789450.2018.1547194. Epub 2018 Nov 15. PMID:30415582 doi:http://dx.doi.org/10.1080/14789450.2018.1547194
  2. ↑ Eguen T, Straub D, Graeff M, Wenkel S. MicroProteins: small size-big impact. Trends Plant Sci. 2015 Aug;20(8):477-82. doi: 10.1016/j.tplants.2015.05.011. Epub, 2015 Jun 23. PMID:26115780 doi:http://dx.doi.org/10.1016/j.tplants.2015.05.011
  3. ↑ Staudt AC, Wenkel S. Regulation of protein function by 'microProteins'. EMBO Rep. 2011 Jan;12(1):35-42. doi: 10.1038/embor.2010.196. Epub 2010 Dec 10. PMID:21151039 doi:http://dx.doi.org/10.1038/embor.2010.196
  4. ↑ Baker EG, Bartlett GJ, Porter Goff KL, Woolfson DN. Miniprotein Design: Past, Present, and Prospects. Acc Chem Res. 2017 Sep 19;50(9):2085-2092. doi: 10.1021/acs.accounts.7b00186., Epub 2017 Aug 23. PMID:28832117 doi:http://dx.doi.org/10.1021/acs.accounts.7b00186
  5. ↑ Chevalier A, Silva DA, Rocklin GJ, Hicks DR, Vergara R, Murapa P, Bernard SM, Zhang L, Lam KH, Yao G, Bahl CD, Miyashita SI, Goreshnik I, Fuller JT, Koday MT, Jenkins CM, Colvin T, Carter L, Bohn A, Bryan CM, Fernandez-Velasco DA, Stewart L, Dong M, Huang X, Jin R, Wilson IA, Fuller DH, Baker D. Massively parallel de novo protein design for targeted therapeutics. Nature. 2017 Oct 5;550(7674):74-79. doi: 10.1038/nature23912. Epub 2017 Sep 27. PMID:28953867 doi:http://dx.doi.org/10.1038/nature23912
  6. ↑ Opella SJ. Relating structure and function of viral membrane-spanning miniproteins. Curr Opin Virol. 2015 Jun;12:121-5. doi: 10.1016/j.coviro.2015.05.006. Epub 2015 , Jun 6. PMID:26057606 doi:http://dx.doi.org/10.1016/j.coviro.2015.05.006
  7. ↑ DiMaio D. Viral miniproteins. Annu Rev Microbiol. 2014;68:21-43. doi: 10.1146/annurev-micro-091313-103727. Epub, 2014 Apr 10. PMID:24742054 doi:http://dx.doi.org/10.1146/annurev-micro-091313-103727
  8. ↑ Kolmar H. Natural and engineered cystine knot miniproteins for diagnostic and therapeutic applications. Curr Pharm Des. 2011 Dec;17(38):4329-36. PMID:22204431

Proteopedia Page Contributors and Editors (what is this?)

Eric Martz, Jaime Prilusky

Retrieved from "http://52.214.119.220/wiki/index.php/User:Eric_Martz/Sandbox_3"
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