| http://purl.uniprot.org/citations/26101839 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26101839 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26101839 | http://www.w3.org/2000/01/rdf-schema#comment | "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 with 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 B-factors derived from MD simulation 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."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2015.06.006"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2015.06.006"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Huang P.S."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Huang P.S."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Mayo S.L."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Mayo S.L."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Thomas L.M."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Thomas L.M."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Mou Y."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/author | "Mou Y."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/pages | "2697-2706"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/pages | "2697-2706"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/title | "Using Molecular Dynamics Simulations as an Aid in the Prediction of Domain Swapping of Computationally Designed Protein Variants."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/title | "Using Molecular Dynamics Simulations as an Aid in the Prediction of Domain Swapping of Computationally Designed Protein Variants."xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/volume | "427"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://purl.uniprot.org/core/volume | "427"xsd:string |
| http://purl.uniprot.org/citations/26101839 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26101839 |
| http://purl.uniprot.org/citations/26101839 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26101839 |