Dissertation/ Thesis
Biophysical studies: Interaction of the Aptamer-protein complexes
| Τίτλος: | Biophysical studies: Interaction of the Aptamer-protein complexes |
|---|---|
| Συγγραφείς: | Heredia Negron, Frances L. |
| Συνεισφορές: | Parés-Matos, Elsie I., College of Arts and Sciences - Sciences, Bauer, William, Ríos-Steiner, Jorge, Ríos-Guillet, Robert, Resto-Irizarry, Pedro J., Department of Chemistry, Rúa de la Asunción, Armando |
| Έτος έκδοσης: | 2022 |
| Συλλογή: | Digital Institutional Repository @UPR (University of Puerto Rico - DiRe.UPR) |
| Θεματικοί όροι: | Aptamer, Biosensors, DNA crystallography, Aptamer-protein complexes, Aptamer’s machine learning, Nucleotides - Analysis, Nucleotide sequence - Data processing, X-ray crystallography, Machine learning, Protein binding |
| Περιγραφή: | Aptamers are synthetic nucleotides used as probes for a plethora of molecules. Their applications include therapeutics, biosensors, drug delivery, among others. Aptamers bind strongly and selectively to a target because of their ability to adopt different three-dimensional structures that form complementary shapes that fit very well into the recognition site. To understand the binding mechanism of Aptamers and to optimize the design of Aptamer-based technologies, it is necessary to understand the details of the Aptamer folding and target interactions from a structural perspective. Unfortunately, while the number of publications of Aptamer applications keeps growing, there is scant research on Aptamers from a structural perspective. This dissertation addresses that knowledge gap by employing two different approaches. The structural characterization of a DNA Aptamer-protein complex using X-ray Crystallography, and the analysis and identification of common patterns within Aptamer sequences using Machine Learning (ML). Two DNA Aptamer-protein pairs were chosen for characterization by X-ray Crystallography: IBA-Insulin and LyApt-Lysozyme. The analysis of the interaction between the DNA Aptamer IBA and Insulin suggests that this Aptamer binds to its target trough the induced-fit model, stabilized by hydrophobic, electrostatic, and non-covalent interactions. Meanwhile in the crystal structure of the DNA Aptamer LyApt and Lysozyme, the Aptamer shows a lack of a folding motif, and the stability of the complex is mainly driven by non-covalent interactions, thus forcing the Aptamer to bind the Lysozyme's heparin binding sites. In both cases, these DNA Aptamers are binding to “hot-spots” within the target proteins. In machine learning analyses, DNA sequences were broken into six nucleotide motifs called 6-mers. From their modeling, it was found that Aptamers have a high “GT” content and the 6-mers with the highest relevance across all ML models were TGG TGG, TGG GGG, GGG GTG, GGT TGG, GCA CAG and GGG GGG. These six 6-mers ... |
| Τύπος εγγράφου: | doctoral or postdoctoral thesis |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | English |
| Relation: | https://hdl.handle.net/20.500.11801/2908 |
| Διαθεσιμότητα: | https://hdl.handle.net/20.500.11801/2908 |
| Rights: | Attribution-NonCommercial-NoDerivs 3.0 United States ; (c) 2022 Frances L. Heredia Negron ; http://creativecommons.org/licenses/by-nc-nd/3.0/us/ |
| Αριθμός Καταχώρησης: | edsbas.F12FE021 |
| Βάση Δεδομένων: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://hdl.handle.net/20.500.11801/2908# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Header | DbId: edsbas DbLabel: BASE An: edsbas.F12FE021 RelevancyScore: 842 AccessLevel: 3 PubType: Dissertation/ Thesis PubTypeId: dissertation PreciseRelevancyScore: 842.276306152344 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Biophysical studies: Interaction of the Aptamer-protein complexes – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Heredia+Negron%2C+Frances+L%2E%22">Heredia Negron, Frances L.</searchLink> – Name: Author Label: Contributors Group: Au Data: Parés-Matos, Elsie I.<br />College of Arts and Sciences - Sciences<br />Bauer, William<br />Ríos-Steiner, Jorge<br />Ríos-Guillet, Robert<br />Resto-Irizarry, Pedro J.<br />Department of Chemistry<br />Rúa de la Asunción, Armando – Name: DatePubCY Label: Publication Year Group: Date Data: 2022 – Name: Subset Label: Collection Group: HoldingsInfo Data: Digital Institutional Repository @UPR (University of Puerto Rico - DiRe.UPR) – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Aptamer%22">Aptamer</searchLink><br /><searchLink fieldCode="DE" term="%22Biosensors%22">Biosensors</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+crystallography%22">DNA crystallography</searchLink><br /><searchLink fieldCode="DE" term="%22Aptamer-protein+complexes%22">Aptamer-protein complexes</searchLink><br /><searchLink fieldCode="DE" term="%22Aptamer%27s+machine+learning%22">Aptamer’s machine learning</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotides+-+Analysis%22">Nucleotides - Analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotide+sequence+-+Data+processing%22">Nucleotide sequence - Data processing</searchLink><br /><searchLink fieldCode="DE" term="%22X-ray+crystallography%22">X-ray crystallography</searchLink><br /><searchLink fieldCode="DE" term="%22Machine+learning%22">Machine learning</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+binding%22">Protein binding</searchLink> – Name: Abstract Label: Description Group: Ab Data: Aptamers are synthetic nucleotides used as probes for a plethora of molecules. Their applications include therapeutics, biosensors, drug delivery, among others. Aptamers bind strongly and selectively to a target because of their ability to adopt different three-dimensional structures that form complementary shapes that fit very well into the recognition site. To understand the binding mechanism of Aptamers and to optimize the design of Aptamer-based technologies, it is necessary to understand the details of the Aptamer folding and target interactions from a structural perspective. Unfortunately, while the number of publications of Aptamer applications keeps growing, there is scant research on Aptamers from a structural perspective. This dissertation addresses that knowledge gap by employing two different approaches. The structural characterization of a DNA Aptamer-protein complex using X-ray Crystallography, and the analysis and identification of common patterns within Aptamer sequences using Machine Learning (ML). Two DNA Aptamer-protein pairs were chosen for characterization by X-ray Crystallography: IBA-Insulin and LyApt-Lysozyme. The analysis of the interaction between the DNA Aptamer IBA and Insulin suggests that this Aptamer binds to its target trough the induced-fit model, stabilized by hydrophobic, electrostatic, and non-covalent interactions. Meanwhile in the crystal structure of the DNA Aptamer LyApt and Lysozyme, the Aptamer shows a lack of a folding motif, and the stability of the complex is mainly driven by non-covalent interactions, thus forcing the Aptamer to bind the Lysozyme's heparin binding sites. In both cases, these DNA Aptamers are binding to “hot-spots” within the target proteins. In machine learning analyses, DNA sequences were broken into six nucleotide motifs called 6-mers. From their modeling, it was found that Aptamers have a high “GT” content and the 6-mers with the highest relevance across all ML models were TGG TGG, TGG GGG, GGG GTG, GGT TGG, GCA CAG and GGG GGG. These six 6-mers ... – Name: TypeDocument Label: Document Type Group: TypDoc Data: doctoral or postdoctoral thesis – Name: Format Label: File Description Group: SrcInfo Data: application/pdf – Name: Language Label: Language Group: Lang Data: English – Name: NoteTitleSource Label: Relation Group: SrcInfo Data: https://hdl.handle.net/20.500.11801/2908 – Name: URL Label: Availability Group: URL Data: https://hdl.handle.net/20.500.11801/2908 – Name: Copyright Label: Rights Group: Cpyrght Data: Attribution-NonCommercial-NoDerivs 3.0 United States ; (c) 2022 Frances L. Heredia Negron ; http://creativecommons.org/licenses/by-nc-nd/3.0/us/ – Name: AN Label: Accession Number Group: ID Data: edsbas.F12FE021 |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsbas&AN=edsbas.F12FE021 |
| RecordInfo | BibRecord: BibEntity: Languages: – Text: English Subjects: – SubjectFull: Aptamer Type: general – SubjectFull: Biosensors Type: general – SubjectFull: DNA crystallography Type: general – SubjectFull: Aptamer-protein complexes Type: general – SubjectFull: Aptamer’s machine learning Type: general – SubjectFull: Nucleotides - Analysis Type: general – SubjectFull: Nucleotide sequence - Data processing Type: general – SubjectFull: X-ray crystallography Type: general – SubjectFull: Machine learning Type: general – SubjectFull: Protein binding Type: general Titles: – TitleFull: Biophysical studies: Interaction of the Aptamer-protein complexes Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Heredia Negron, Frances L. – PersonEntity: Name: NameFull: Parés-Matos, Elsie I. – PersonEntity: Name: NameFull: College of Arts and Sciences - Sciences – PersonEntity: Name: NameFull: Bauer, William – PersonEntity: Name: NameFull: Ríos-Steiner, Jorge – PersonEntity: Name: NameFull: Ríos-Guillet, Robert – PersonEntity: Name: NameFull: Resto-Irizarry, Pedro J. – PersonEntity: Name: NameFull: Department of Chemistry – PersonEntity: Name: NameFull: Rúa de la Asunción, Armando IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2022 Identifiers: – Type: issn-locals Value: edsbas – Type: issn-locals Value: edsbas.oa |
| ResultId | 1 |