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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===User Interface & Color Key===
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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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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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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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*2011 review <ref>PMID: 21151039</ref>
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*Links do not work.
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*[&#10003;] represents a checkbox. When checked, it will color the chain 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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===Mini===
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<b>Before expanding this section, it could look like this:</b>
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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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<table border="0" cellspacing="0" cellpadding="2" width="330">
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*2017: De novo designed: <ref>PMID: 28953867</ref>
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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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*2015: Viruses have hydrophobic, membrane-spanning miniproteins. <ref>PMID: 26057606</ref> <ref>PMID: 24742054</ref>
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<b>After expanding, it could look like this:</b>
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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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<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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==In Proteopedia==
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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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*There are about 60 entries found with a search for "miniprotein" (but no such category).
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<font color="#009000"><b>Hide all conservation colors.</b></font>
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*[[:Category:Microprotein]] has 3 entries, and [[:Category:Hybrid microprotein]] has 1.
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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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<!-- &nbsp;[&#10003;]A [&#10003;]C<br>&nbsp;[&#10003;]B [&#10003;]D -->
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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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==References==
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<references />
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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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# insert allRenderingsOff script (already in use for NMR)
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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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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>2hhd_consurf.spt</b>
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<br>
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In the example of 2hhd, there are two sets of sequence-identical chains (AC, BD). Each set has a block of amino acid selections for each color grade. The amino acids per color grade are combined for all chains (including sequence-different chains) as shown in the example script below. This script was run to produce the scene above <i>Consurf color all chains</i>.
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<tt><pre>
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select none
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select selected and (:A,:C)
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define ~con10 selected
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select PHE71, PHE85, PHE118
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select selected and (:B,:D)
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select selected or ~con10
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define con10 selected
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color [255,255,150]
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spacefill
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select LYS7, LYS16, GLU27, ARG31, PHE33, PRO37, THR39, LYS40, THR41, PHE43
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select selected or SER52, HIS58, GLY59, LYS61, VAL62, ALA65, ALA69, LEU83, SER84
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select selected or HIS87, ALA88, LEU91, ARG92, VAL93, ASP94, PRO95, ASN97, PHE98
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select selected or LEU101, HIS122, SER124, ASP126, LYS127, VAL132, LEU136
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select selected or LYS139, TYR140, ARG141
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select selected and (:A,:C)
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define ~con9 selected
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select VAL1, GLU7, LYS8, TRP15, GLY24, ARG30, LEU32, VAL34, TYR35, PRO36, TRP37
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select selected or THR38, ARG40, PHE42, PHE45, GLY46, SER49, ALA53, ASN57, VAL60
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select selected or ALA62, HIS63, GLY64, LYS66, VAL67, ASP79, LEU81, LYS82, LEU88
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select selected or SER89, GLU90, HIS92, LEU96, VAL98, PRO100, ASN102, PHE103
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select selected or LEU106, PHE122, GLN127, LYS132, VAL137, ALA140, TYR145
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select selected or HIS146
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select selected and (:B,:D)
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select selected or ~con9
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define ~con9 selected
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color [160,37,96]
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spacefill
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select VAL1, LEU2, SER3, ASP6, GLY25, LEU29, TYR42, HIS45, PHE46, ASP47, GLY51
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select selected or GLN54, ASP74, ASP85, LEU86, VAL96, LYS99, HIS112, THR118
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select selected or PRO119, ALA123, PHE128, VAL135
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select selected and (:A,:C)
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define ~con8 selected
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select VAL18, LEU28, GLN39, PHE41, ASP47, LEU48, LEU91, CYS93, ASP94, HIS97
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select selected or ASP99, GLU101, LEU105, GLY107, ASN108, ALA115, ALA129, ALA138
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select selected or LEU141
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select selected and (:B,:D)
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select selected or ~con8
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define ~con8 selected
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color [240,125,171]
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spacefill
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select MET32, LEU66, ASP75, ALA79, LEU80, HIS103, VAL107, THR108, ALA110, PHE117
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select selected or THR137, SER138
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select selected and (:A,:C)
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define ~con7 selected
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select VAL11, LYS17, GLU26, ALA27, GLY29, LEU31, THR84, LYS95, GLN131, VAL134
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select selected and (:B,:D)
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select selected or ~con7
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define ~con7 selected
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color [250,201,222]
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spacefill
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select TRP14, ALA28, PRO44, LYS60, HIS72, SER81, LYS90, SER102, CYS104, SER133
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select selected and (:A,:C)
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define ~con6 selected
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select HIS2, LEU3, VAL33, ALA70, GLY74, HIS77, ALA86, VAL113, LEU114, THR123
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select selected or PRO124, LYS144
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select selected and (:B,:D)
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select selected or ~con6
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define ~con6 selected
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color [252,237,244]
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spacefill
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select VAL17, ALA26, PHE36, LYS56, VAL70, LEU100, LEU106, VAL121
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select selected and (:A,:C)
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define ~con5 selected
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select THR4, ASN19, LYS65, ASN80, VAL111, ALA128, VAL133, GLY136, HIS143
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select selected and (:B,:D)
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select selected or ~con5
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define ~con5 selected
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color [255,255,255]
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spacefill
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select HIS20, ALA21, LEU48, SER49, MET76, PRO77, LEU109, ALA120
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select selected and (:A,:C)
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define ~con4 selected
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select GLU6, THR50, VAL54, LYS59, LEU68, SER72, HIS117
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select selected and (:B,:D)
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select selected or ~con4
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define ~con4 selected
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color [234,255,255]
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spacefill
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select ASN9, VAL10, LYS11, SER35, THR38, HIS50, VAL55, HIS89, LEU125, ALA130
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select selected or THR134
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select selected and (:A,:C)
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define ~con3 selected
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select VAL20, MET55, LYS61, VAL109, ALA142
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select selected and (:B,:D)
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select selected or ~con3
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define ~con3 selected
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color [215,255,255]
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spacefill
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select GLU30, ALA53, THR67, ALA71, ALA82, LEU105, PRO114, LEU129
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select selected and (:A,:C)
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define ~con2 selected
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select GLY25, LEU75, ALA76, LYS120, GLU121
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select selected and (:B,:D)
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select selected or ~con2
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define ~con2 selected
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color [140,255,255]
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spacefill
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select PRO4, ALA5, THR8, ALA12, ALA13, GLY15, GLY18, ALA19, GLY22, GLU23, TYR24
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select selected or LEU34, GLY57, ALA63, ASP64, ASN68, VAL73, ASN78, ALA111
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select selected or LEU113, ALA115, GLU116, SER131
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select selected and (:A,:C)
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define ~con1 selected
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select PRO5, SER9, ALA10, THR12, ALA13, LEU14, GLY16, ASP21, GLU22, VAL23, GLU43
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select selected or SER44, PRO51, ASP52, GLY56, PRO58, GLY69, ASP73, LEU78, GLY83
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select selected or THR87, ARG104, LEU110, CYS112, HIS116, GLY119, PRO125, VAL126
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select selected or TYR130, ALA135, ASN139
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select selected and (:B,:D)
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select selected or ~con1
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define ~con1 selected
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color [16,200,209]
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spacefill
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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

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