View source for 4zn8


==Using molecular dynamics simulations to predict domain swapping of computationally designed protein variants==
<StructureSection load='4zn8' size='340' side='right'caption='[[4zn8]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zn8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZN8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ndj|4ndj]], [[4ndk|4ndk]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zn8 OCA], [http://pdbe.org/4zn8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zn8 RCSB], [http://www.ebi.ac.uk/pdbsum/4zn8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zn8 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In standard implementations of computational protein design, a positive-design approach is used to predict sequences that will be stable on a given backbone structure. Possible competing states are typically not considered, primarily because appropriate structural models are not available. One potential competing state, the domain-swapped dimer, is especially compelling because it is often nearly identical to its monomeric counterpart, differing by just a few mutations in a hinge region. Molecular dynamics (MD) simulations provide a computational method to sample different conformational states of a structure. Here, we tested whether MD simulations could be used as a post-design screening tool to identify sequence mutations leading to domain-swapped dimers. We hypothesized that a successful computationally-designed sequence would have backbone structure and dynamics characteristics similar to that of the input structure, and that in contrast, domain-swapped dimers would exhibit increased backbone flexibility and/or altered structure in the hinge-loop region to accommodate the large conformational change required for domain swapping. While attempting to engineer a homodimer from a 51 amino acid fragment of the monomeric protein engrailed homeodomain (ENH), we had instead generated a domain-swapped dimer (ENH_DsD). MD simulations on these proteins showed increased MD simulation derived B factors in the hinge loop of the ENH_DsD domain-swapped dimer relative to monomeric ENH. Two point mutants of ENH_DsD designed to recover the monomeric fold were then tested with an MD simulation protocol. The MD simulations suggested that one of these mutants would adopt the target monomeric structure, which was subsequently confirmed by X-ray crystallography.

Using molecular dynamics simulations as an aid in the prediction of domain swapping of computationally designed protein variants.,Mou Y, Huang PS, Thomas LM, Mayo SL J Mol Biol. 2015 Jun 20. pii: S0022-2836(15)00346-0. doi:, 10.1016/j.jmb.2015.06.006. PMID:26101839<ref>PMID:26101839</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4zn8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drome]]
[[Category: Large Structures]]
[[Category: Huang, P S]]
[[Category: Mayo, S L]]
[[Category: Thomas, L M]]
[[Category: Computational protein design]]
[[Category: De novo protein]]
[[Category: Domain-swapped dimer]]