| fullrecord |
[{"key": "dc.contributor.advisor", "value": "Hyt\u00f6nen, Vesa", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Yl\u00e4nne, Jari", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Mykuliak, Vasyl", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Palmujoki, Lassi", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2023-02-21T07:07:31Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2023-02-21T07:07:31Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2022", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/85558", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Fyysisi\u00e4 voimia k\u00e4sittelev\u00e4 molekyylibiologian alue on nopeasti kehittym\u00e4ss\u00e4, johtuen sek\u00e4 tietokoneiden laskentakapasiteetin kasvusta ett\u00e4 kehityksist\u00e4 teoreettisilla rintamilla kuten molekyylij\u00e4rjestelmien laskennallisessa simulaatiossa \u2013 eritoten ohjatun molekyyli-dynamiikan (steered molecular dynamics, SMD) ja sen kaltaisten menetelmien osalta. SMD mahdollistaa samankaltaisen, mutta osaltaan yksityiskohtaisemman tavan tarkastella molekyylien sitoutumista ja irtoamista verrattuna kokeellisiin menetelmiin, kuten atomivoimamikroskooppi ja magneettiset pinsetit (magnetic tweezers). Tietokoneiden laskentakapasiteetin rajat tulevat kuitenkin (toistaiseksi) vastaan siin\u00e4 m\u00e4\u00e4rin, ett\u00e4 voimien on oltava useita suuruusluokkia suurempia kuin kokeellisissa menetelmiss\u00e4. Osaltaan t\u00e4st\u00e4 johtuu, ett\u00e4 m\u00e4\u00e4r\u00e4llisi\u00e4 tuloksia on joko eritt\u00e4in vaikea, ellei mahdoton saada. Vaikkakin tulokset ovat laadullisia, tietoa t\u00e4sm\u00e4llisest\u00e4 atomitason vuorovaikutusten kehityksest\u00e4 on mahdollista saada, ja t\u00e4m\u00e4 tieto on mielek\u00e4st\u00e4 my\u00f6s kokeen viitekehyksen ulkopuolella. T\u00e4ss\u00e4 tutkimuksessa k\u00e4sitell\u00e4\u00e4n SMD:ll\u00e4 m\u00e4\u00e4ritetty\u00e4 vuorovaikutusten kehityst\u00e4 kahden proteiinin, taliini-1:n ja integriini beta3:n, v\u00e4lill\u00e4; tarkemmin ottaen taliini-1:n FERM-laskoksisen p\u00e4\u00e4domeenin ja integriini beta3:n sytoplasmisen h\u00e4nt\u00e4domeenin v\u00e4lill\u00e4. Tutkielma pyrkii vastaamaan kahteen tutkimusongelmaan: 1) Onko SMD:ll\u00e4 m\u00e4\u00e4ritetty vetovoima (pulling force) yksi- vai monivaiheinen prosessi? Eli kuinka monta energiakynnyst\u00e4 on vetovoimakuvaajassa? 2) Tarkasteltaessa taliinin ja integriinin irtoamisprosessia k\u00e4\u00e4nteisess\u00e4 suunnassa (eli niiden sitoutumisprosessia), korreloiko t\u00e4m\u00e4 sitoutumisprosessi aiemmin esitetyn sitoutumisprosessin kanssa? T\u00e4m\u00e4 on toinen tutkimus, joka hy\u00f6dynt\u00e4\u00e4 samankaltaista laskennallista menetelm\u00e4\u00e4 (SMD) kyseisen proteiinivuorovaikuksen analyysiin. Kuitenkin parhaan tietomme mukaan taliini-1:n FERM-rakenne vastaa nyt paremmin biologisesti ilmenev\u00e4\u00e4 rakennetta kuin aikaisemmissa tutkimuksissa. Sen lis\u00e4ksi, toisin kuin aikaisemmissa vastaavissa tutkimuksissa, t\u00e4ss\u00e4 tutkimuksessa hy\u00f6dynnet\u00e4\u00e4n integriini beta3:n koko sytoplasmista h\u00e4nt\u00e4domeenia yhdist\u00e4m\u00e4ll\u00e4 kalvol\u00e4heisen (membrane proximal) ja kalvokaukaisen (membrane distal) osan eri kristallografiarakenteista. Taliini-1-integriini beta3-vuorovaikutuksen SMD-simulaatio vaikuttaa olevan kaksiaskelinen prosessi. Ensimm\u00e4inen energiakynnys vastaa kalvol\u00e4heisen osan irtoamista taliinista, kun taas integriinin NPLY-osan irtoaminen osuu toisen energiakynnyksen kohdalle. Liikeradan tarkastelu k\u00e4\u00e4nteisess\u00e4 suunnassa tukee aiemmin ehdotettua hypoteesia, ett\u00e4 taliini-integriini-vuorovaikutus perustuu alustavaan NPLY-osan sitoutumiseen, jota seuraa kalvol\u00e4heisen osan sitoutuminen taliiniin.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The area of molecular biology dealing with physical forces is a rapidly advancing field, thanks to technology that is getting faster and improvements in theoretical fronts like computational simulations of molecular systems - particularly steered molecular dynamics (SMD) simulations and related methods. SMD allows similar and extended ways to study molecular (un)binding and (un)folding processes like atomic force microscopy (AFM) and magnetic tweezers. However, due to limitations in computer hardware (for the time being) the forces are several orders of magnitude larger than those observed with experimental methods and, unfortunately, quantitative results are either very challenging or impossible to acquire. Being qualitative in nature, however, information on the precise atom-level evolution of molecular interactions can be obtained that is also meaningful outside the context of a single experiment. This study deals with the evolution of interactions, as determined by SMD, between proteins talin-1 and integrin beta3, particularly the interaction between talin-1 FERM-folded head domain and the cytoplasmic segment of integrin beta3. The study aimed to answer two research questions: 1) Is the pulling force acquired from SMD simulations a single- or multi-step process? In other words, how many energy barriers does the pulling force profile contain? 2) When observing the unbinding process for talin and integrin in reverse (i.e., binding), does this binding process correlate to the previously proposed binding model? This is the second study to utilize the similar computational method (SMD) for the analysis of that particular interaction. However and to the best of our knowledge, the talin-1 FERM structure used in this study better resembles a biologically existing talin structure than those used in previous studies. Also, in contrast to previous studies, the whole cytoplasmic segment of integrin beta3 is utilized in this study, which results from combining the membrane proximal and membrane distal parts of integrin beta3 from different crystallographic structures. The SMD simulations of the unbinding and unfolding of talin1-integrin beta3 interaction suggest a two-step process. The first energy barrier, observed as a peak in the pulling force profile, corresponds to the unbinding of the membrane proximal helix, which becomes unstable and unfolds under load during unbinding. The unbinding of the NPLY motif in the membrane distal part is, likewise, associated with the second energy barrier. When observing the trajectory in reverse the results support the previously proposed hypothesis that the talin-integrin interaction is based on the initial binding of the NPLY motif followed by the binding of the membrane proximal segment of integrin to talin.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2023-02-21T07:07:31Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2023-02-21T07:07:31Z (GMT). No. of bitstreams: 0\n Previous issue date: 2022", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "49", "language": "", "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": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "computational biology", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "mechanobiology", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "SMD simulation of talin and integrin interaction : role of membrane proximal and distal integrin segments in talin binding", "language": "", "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-202302211817", "language": "", "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": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "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": "yvv.contractresearch.funding", "value": "0", "language": "", "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": "openAccess", "language": null, "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": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "integriinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteiinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "molekyylidynamiikka", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "solubiologia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "simulointi", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "vuorovaikutus", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "taliini", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "dynamiikka", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "integrins", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteins", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "molecular dynamics", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "cell biology", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "simulation", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "interaction", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "talin", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "dynamics", "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.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
|