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[{"key": "dc.contributor.advisor", "value": "Pentik\u00e4inen, Olli", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Niinivehmas, Sanna", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Kuusisto, Mira", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2016-06-20T07:00:52Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2016-06-20T07:00:52Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2016", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1545458", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/50440", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Sytokromi P450 (CYP) -entsyymit ovat p\u00e4\u00e4asiallisia katalyyttej\u00e4 ihmisen vaiheen 1 vierasainemetaboliassa. CYP-v\u00e4litteisen metabolian ennustaminen on t\u00e4rke\u00e4 osa kemikaalien ja erityisesti l\u00e4\u00e4keaineiden kehityst\u00e4, sill\u00e4 metabolian seurauksena vierasaine voi muuttua keholle haitalliseksi yhdisteeksi, tai l\u00e4\u00e4keaine voi menett\u00e4\u00e4 terapeuttisen vaikutuksensa liian nopean metabolian vuoksi. T\u00e4m\u00e4n tutkimuksen tavoite oli kehitt\u00e4\u00e4 tarkka, nopea ja aiempaa luotettavampi menetelm\u00e4 CYP alatyypin 2A6 katalysoimien pienmolekyylien metaboliakohtien ennustukseen. Tavoitteen saavuttamiseksi tutkimuksessa kehitettiin uusia rakenne- ja ligandipohjaisia l\u00e4hestymistapoja yhdist\u00e4vi\u00e4 menetelmi\u00e4 CYP2A6-substraattien metaboliakohtien ennustukseen. Kehitettyj\u00e4 menetelmi\u00e4 vertailtiin erilaisiin ligandi- ja rakennepohjaisiin menetelmiin. Luotettavin kehitetty yhdistelm\u00e4menetelm\u00e4 ennustaa CYP2A6-substraatille yhden metaboliakohdan 77 % todenn\u00e4k\u00f6isyydell\u00e4, mik\u00e4 on 5 ja 12 prosenttiyksikk\u00f6\u00e4 korkeampi kuin parhailla testatuilla ligandi- tai rakennepohjaisilla menetelmill\u00e4 yksin\u00e4\u00e4n. Metaboliakohdan lis\u00e4ksi menetelm\u00e4 ennustaa substraatin aktiivisen konformaation CYP2A6:n sitoutumistaskussa. Kehitetty menetelm\u00e4 on mahdollista laajentaa my\u00f6s muille CYP-alatyypeille pienill\u00e4 parametrien muutoksilla. Malli voi tarjota arvokasta tietoa CYP-v\u00e4litteisen metabolian mekanismeista ja rakenteellisesta perustasta. Menetelm\u00e4\u00e4 voidaan k\u00e4ytt\u00e4\u00e4 yhdess\u00e4 muiden laskennallisten tai kokeellisten mallien kanssa kemikaalien tai l\u00e4\u00e4keainekandidaattien rakenteen optimointiin metabolian kannalta toivotumpaan suuntaan.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Cytochrome P450 (CYP) enzymes are the main catalysts in human phase 1 metabolism of exogenous compounds such as drugs. Since metabolic reactions can result in toxic metabolites or poor bioavailability of drugs, prediction of CYP-mediated metabolism is an important field in drug and chemical development. The goal of this study was to develop an accurate and fast method with improved reliability for prediction of sites of metabolism of small molecules catalysed by CYP subtype 2A6. In order to achieve the goal, several new methods combining both ligand- and structure-based approaches were developed for prediction of sites of metabolism of CYP2A6 substrates. The new methods were compared to varying ligand- or structure-based methods. The most reliable one of the developed ligand- and structure-based methods predicts one site of metabolism for a CYP2A6 substrate with 77% probability, which is 5 and 12 percent units higher than with the best ligand- or structure-based methods alone. Not only does the new method predict the site of metabolism with considerable reliability, but also the active conformation of a substrate in the binding site of CYP2A6. With subtype-specific parametrization, the method is also expandable to other subtypes of CYP enzymes. The method may provide valuable information about the mechanisms and structural basis of CYP-mediated metabolism. The method can be used in combination with other computational or experimental approaches to optimize structures of environmental compounds or drug candidates towards more desirable metabolic profiles.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Mira Kuusisto (mimakrku) on 2016-06-20 07:00:49.232068. Form: Pro gradu -lomake (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake). JyX data: [jyx_publishing-allowed (fi) =False]", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija.group@korppi.jyu.fi) on 2016-06-20T07:00:52Z\nNo. of bitstreams: 2\nURN:NBN:fi:jyu-201606203212.pdf: 29528549 bytes, checksum: ef4e4e0643351517be2bfde2246028d8 (MD5)\nlicense.html: 1193 bytes, checksum: 1ee1ef7a6df4ac5281ec0b8aa18b3149 (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2016-06-20T07:00:52Z (GMT). No. of bitstreams: 2\nURN:NBN:fi:jyu-201606203212.pdf: 29528549 bytes, checksum: ef4e4e0643351517be2bfde2246028d8 (MD5)\nlicense.html: 1193 bytes, checksum: 1ee1ef7a6df4ac5281ec0b8aa18b3149 (MD5)\n Previous issue date: 2016", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (46 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.title", "value": "Luotettava laskennallinen menetelm\u00e4 sytokromi P450 alatyypin 2A6 katalysoimien pienmolekyylien metaboliakohtien ennustukseen", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201606203212", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.date.updated", "value": "2016-06-20T07:00:53Z", "language": null, "element": "date", "qualifier": "updated", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": null, "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": "fi", "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": null, "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sytokromit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "aineenvaihdunta", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biokemia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Aineistoon p\u00e4\u00e4sy\u00e4 on rajoitettu tekij\u00e4noikeussyist\u00e4. Aineisto on luettavissa Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6asemalta. Ks. https://kirjasto.jyu.fi/fi/tyoskentelytilat/laitteet-ja-tilat.", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "This material has a restricted access due to copyright reasons. It can be read at the workstation at Jyv\u00e4skyl\u00e4 University Library reserved for the use of archival materials: https://kirjasto.jyu.fi/en/workspaces/facilities.", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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