{"id":26,"date":"2018-04-25T12:06:15","date_gmt":"2018-04-25T10:06:15","guid":{"rendered":"https:\/\/site.uit.no\/cube\/?page_id=26"},"modified":"2018-05-07T11:38:08","modified_gmt":"2018-05-07T09:38:08","slug":"about","status":"publish","type":"page","link":"https:\/\/site.uit.no\/cube\/about\/","title":{"rendered":"Project"},"content":{"rendered":"

CUBE3<\/span><\/h3>\n

C<\/strong><\/span>omputational\u00a0U<\/strong><\/span>nderstanding of\u00a0B<\/strong><\/span>iocatalytic\u00a0E<\/strong><\/span>volution to\u00a0E<\/strong><\/span>xtreme\u00a0E<\/strong><\/span>nvironments<\/h4>\n
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\"\"The project will focus on evolutionary principles behind adaptation to extreme environments with\u00a0emphasis on how temperature affects the stability and activity of enzymes and ribosomes. This will be\u00a0achieved by connecting the underlying microscopic energetics of the macromolecular structures with\u00a0macroscopic observables using computational approaches pioneered by Brandsdal and \u00c5qvist. Predictions\u00a0made with computations will then be tested and verified by experiments. The contribution to the free energy\u00a0from enthalpy and entropy remains highly challenging to calculate, particularly when dealing with large\u00a0complex biological macromolecules involved in catalysis and binding events. The core activities of CUBE3\u00a0are centered on suggested hypothesis of how evolution changes the enthalpy-entropy balance\u00a0to allow enzymes to function near the freezing point of water, as discussed in our recent publication in\u00a0Nature Reviews of Chemistry<\/a>. The interest in enzymes from extremophiles is also immense from an\u00a0industrial and biotechnological point of view, due to their potential use as biocatalysts either in their natural\u00a0form or engineered variants<\/p>\n

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The primary objective of CUBE3 is to understand the principles responsible for the universal\u00a0enthalpy-entropy changes involved in temperature adaptation of biocatalysts. Secondary objectives are to 1)\u00a0calculate the thermodynamic activation parameters of enzymes and ribosomes, 2) develop computational\u00a0tools to disentangle activity and stability mutations, 3) develop methods for understanding of the temperature\u00a0dependence of substrate binding, 4) create, develop and validate experimental data and computational\u00a0models on catalytic activity and stability, and 5) provide new software to the international community at no\u00a0cost. This objective will be reached through five work packages:<\/p>\n

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  1. Temperature dependence of catalytic rates of different thermally adapted enzyme orthologues and\u00a0ribosomes (read more<\/a>).<\/li>\n
  2. Develop computational tools and protocols to pinpoint residual hot spots important to thermal\u00a0stability (read more<\/a>).<\/li>\n
  3. Develop computational tools and protocols to enable calculation of free energies, enthalpies and\u00a0entropies of substrate binding (read more<\/a>).<\/li>\n
  4. Experimental characterization and design (read more<\/a>).<\/li>\n
  5. Visualization and analysis of large data sets (read more<\/a>).<\/li>\n<\/ol>\n

     <\/p>\n

    The project is carried out at the Troms\u00f8 node\u00a0of the\u00a0Hylleraas Cente for Quantum Molecular Sciences<\/a>, a new Centre of Excellence\u00a0establishe for a 10-year period 2017-2027.\u00a0The Hylleraas Centre gathers world-leading\u00a0expertise in the domains of electronic-structure theory, multiscale modelling, computational spectroscopy,\u00a0and the use of computation to understand and control complex chemical and biological systems. Through an\u00a0extensive incoming sabbatical programme, a generous visitors programme, focus bienniums, international\u00a0workshops, conferences, outreach activities and seminar series, the Hylleraas Centre will create an\u00a0internationally visible and attractive centre for the computational modelling and understanding of new\u00a0chemistry at the frontiers of a wide range of scientific disciplines.<\/p>\n","protected":false},"excerpt":{"rendered":"

    CUBE3 Computational\u00a0Understanding of\u00a0Biocatalytic\u00a0Evolution to\u00a0Extreme\u00a0Environments The project will focus on evolutionary principles behind adaptation to extreme environments with\u00a0emphasis on how temperature affects the stability and activity of enzymes and ribosomes. This will be\u00a0achieved by connecting the underlying microscopic energetics of the … Continued<\/a><\/p>\n","protected":false},"author":862,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-fullwidth.php","meta":{"footnotes":""},"class_list":["post-26","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/pages\/26","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/users\/862"}],"replies":[{"embeddable":true,"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/comments?post=26"}],"version-history":[{"count":18,"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/pages\/26\/revisions"}],"predecessor-version":[{"id":241,"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/pages\/26\/revisions\/241"}],"wp:attachment":[{"href":"https:\/\/site.uit.no\/cube\/wp-json\/wp\/v2\/media?parent=26"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}