{"id":4265,"date":"2018-08-16T17:59:15","date_gmt":"2018-08-16T16:59:15","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=4265"},"modified":"2018-08-16T17:59:15","modified_gmt":"2018-08-16T16:59:15","slug":"ismb-2018-chicago-summary-of-interesting-talks-posters","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2018\/08\/ismb-2018-chicago-summary-of-interesting-talks-posters\/","title":{"rendered":"ISMB 2018 (Chicago): Summary of Interesting Talks\/Posters"},"content":{"rendered":"
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Catherine’s Selection<\/em><\/p>\n

Network approach integrates 3D structural and sequence data to improve protein structural comparison<\/strong><\/p>\n<\/div>\n

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Why<\/strong>: Current graph mapping in protein structural comparison ignores sequence order of residues. Residues distant in sequence but close in 3D space are more important.
\nHow<\/strong>: Introduce sequence order of residues, set a sequence-distance cutoff to consider structurally important residues, count the graphlet frequency and embed into PCA space.
\nResults<\/strong>: the new method is predictive of SCOP and CATH \u2018groups\u2019. Certain graphlets are enriched in alpha and beta folds.
\nLink<\/strong>: https:\/\/www.nature.com\/articles\/s41598-017-14411-y<\/a><\/p>\n

Investigating the molecular determinants of Ebola virus pathogenicity<\/strong><\/p>\n

Why<\/strong>: Reston virus is the only Ebola virus that is not pathogenic to human
\nWhat they do<\/strong>: multiple sequence alignment to look for specificity determining positions (SDPs) using s3det, then predict the effect of each individual SDP on the stability of the protein with mCSM.
\nResults<\/strong>: VP40 SDPs alter octamer formation, structure hydrophobic core. VP24 SDPs leads to impair binding to KPNA5 in human, which inhibits interferon signalling.
\nImpact<\/strong>: only a few SDPs distinguish Reston VP24 from VP24 of others. Human-pathogenic Reston viruses may emerge.
\nLink<\/strong>: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5558184\/#__ffn_sectitle<\/a><\/p>\n

Computational Analysis Highlights Key Molecular Interactions and Conformational Flexibility of a New Epitope on the Malaria Circumsporozoite Protein and Paves the Way for Vaccine Design<\/strong><\/p>\n

Why<\/strong>: An antibody with a strong binding affinity was found in a group of subjects. This antibody prevents cleavage of the surface protein.
\nWhat they do<\/strong>: They found the linear epitope, crystallise the strong and medium binders and run a molecular dynamic simulation to find out the flexibility of the structures.
\nResults<\/strong>: The strong binder is less flexible. Moreover, the strong binder is similar to the germline sequence which may mean that this antibody could have been readily formed.
\nLink<\/strong>: https:\/\/www.nature.com\/articles\/nm.4512<\/a><\/p>\n

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\nMatt’s Selection<\/em><\/p>\n

\u201cAnalysis of sequence and structure data to understand nanobody architectures and antigen interactions\u201d<\/strong>
\nLaura S. Mitchell (Colwell Group)<\/strong>
\nUniversity of Cambridge, UK<\/strong><\/p>\n

This poster detailed the work from Laura\u2019s two most recent publications, which can be found here: https:\/\/doi.org\/10.1002\/prot.25497<\/a>, <\/span><\/span><\/span>https:\/\/doi.org\/10.1093\/protein\/gzy017<\/a><\/span><\/span><\/span><\/p>\n

They describe a comprehensive analysis of the binding properties of the 156 non-redundant nanobody-antigen (Nb-Ag) complexes in the PDB\/SAbDab (October 2017). Their analyses include Nb sequence variability (both global and across the binding regions), contact maps of nanobody-<\/span><\/span><\/span>antigen <\/span><\/span><\/span>interactions by region, and the <\/span><\/span><\/span>typical <\/span><\/span><\/span>chemical properties of <\/span><\/span><\/span>each <\/span><\/span><\/span>paratope. Nb-Ag complexes<\/span><\/span><\/span> are compared to a reference set of monoclonal antibody-antigen (mAb-Ag) complexes. This work is a key first step in advancing our understanding of Nb paratopes, and will aid the development of new diagnostics and therapeutics.
\n<\/span><\/span><\/span><\/p>\n

\u201c<\/strong>OSPREY 3.0: Open-Source Protein Redesign for You, with Powerful New Features\u201d<\/strong>
\nJeffrey W. Martin (Donald Group)<\/strong>
\nDuke University, USA<\/strong><\/p>\n

OSPREY 3.0 (https:\/\/www.biorxiv.org\/content\/early\/2018\/04\/23\/306324<\/a>) represents a large advance towards time-efficient continuous flexibility modelling of protein-protein interfaces.<\/p>\n

Its new algorithms LUTE and BBK* allow for continuous rotamer flexibility searching and entropy-aware binding constant approximation in a much more efficient manner. The CATS algorithm also introduces local backbone flexibility as a long-awaited feature. <\/span><\/span><\/span>This software now has a easy-to-use Python interface, and is fully Open-Source, making it an extremely attractive <\/span><\/span><\/span>alternative <\/span><\/span><\/span>to <\/span><\/span><\/span>other <\/span><\/span><\/span>proprietary <\/span><\/span><\/span>protein design t<\/span><\/span><\/span>ools.<\/span><\/span><\/span><\/p>\n

\u201cFunctional annotation of chemical libraries across diverse biological processes\u201d
\n<\/strong>Scott Simpkins<\/strong>
\nUniversity of Minnesota-Twin Cities, USA<\/strong><\/p>\n

This interesting talk detailed the work published in Nature Chemical Biology in September 2017 (https:\/\/doi.org\/10.1038\/nchembio.2436<\/a>).<\/p>\n

310 yeast gene-deletion mutants were isolated to perform chemical-genetic profile studies across six diverse small molecule high-throughput screening libraries<\/span><\/span><\/span>. By studying which gene-deletion mutants were hypersensitive or resistant to each compound, the researchers could assign most members of each chemical library a <\/span><\/span><\/span>probable <\/span><\/span><\/span>functional annotation. Mapping back to gene-interaction profile <\/span><\/span><\/span>data<\/span><\/span><\/span> also <\/span><\/span><\/span>allowed them to <\/span><\/span><\/span>infer likely targets <\/span><\/span><\/span>for some compounds. The GO <\/span><\/span><\/span>annotations <\/span><\/span><\/span>associated with these genes <\/span><\/span><\/span>could then be used <\/span><\/span><\/span>assess whether a given starting library is likely to<\/span><\/span><\/span> contain promising starting-points <\/span><\/span><\/span>that<\/span><\/span><\/span> affect a given biological function<\/span><\/span><\/span>. For example, the authors highlight<\/span><\/span><\/span>ed<\/span><\/span><\/span> a deficiency <\/span><\/span><\/span>across all<\/span><\/span><\/span> libraries <\/span><\/span><\/span>against the<\/span><\/span><\/span> cellular processes of cytokinesis <\/span><\/span><\/span>and<\/span><\/span><\/span> ribosome biogenesis. <\/span><\/span><\/span>Conversely, they<\/span><\/span><\/span> found <\/span><\/span><\/span>a <\/span><\/span><\/span>large enrichment <\/span><\/span><\/span>across all libraries for compounds<\/span><\/span><\/span> likely to affect <\/span><\/span><\/span>g<\/span><\/span><\/span>lycosylation or cell wall biogenesis. <\/span><\/span><\/span>Compounds that target transcription and chromatin organisation were found to be enriched in certain datasets, and depleted in others. This genre of profiling provides researchers a way of <\/span><\/span><\/span>judging<\/span><\/span><\/span> a priori<\/i><\/span><\/span><\/span> whether a given screening library is likely to contain promising lead compounds, given the functional role of the target of interest.
\n<\/span><\/span><\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Catherine’s Selection Network approach integrates 3D structural and sequence data to improve protein structural comparison Why: Current graph mapping in protein structural comparison ignores sequence order of residues. Residues distant in sequence but close in 3D space are more important. How: Introduce sequence order of residues, set a sequence-distance cutoff to consider structurally important residues, […]<\/p>\n","protected":false},"author":45,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","wikipediapreview_detectlinks":true,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"ngg_post_thumbnail":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[52,10,30,48,9],"tags":[],"ppma_author":[532],"class_list":["post-4265","post","type-post","status-publish","format-standard","hentry","category-conferences","category-groupmeetings","category-links","category-publication","category-talks"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":532,"user_id":45,"is_guest":0,"slug":"matt","display_name":"Matthew Raybould","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/71f525eb0d7861fad46de36f6b8f3a4cfd89c5cc6b13e48c5dc6e79a82c5b591?s=96&d=mm&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/4265","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/users\/45"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=4265"}],"version-history":[{"count":5,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/4265\/revisions"}],"predecessor-version":[{"id":4271,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/4265\/revisions\/4271"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=4265"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=4265"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=4265"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=4265"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}