دورية أكاديمية
Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis
| العنوان: | Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis |
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| المؤلفون: | Barrera Guisasola, Exequiel Ernesto, Gutierrez, Lucas Joel, Salcedo, Rodrigo Emiliano, Garibotto, Francisco Matías, Andujar, Sebastian Antonio, Enriz, Ricardo Daniel, Rodríguez, Ana M. |
| بيانات النشر: | Elsevier |
| المجموعة: | CONICET Digital (Consejo Nacional de Investigaciones Científicas y Técnicas) |
| مصطلحات موضوعية: | AMYLOID β-PEPTIDE, MIMETIC PEPTIDE INHIBITOR, MM-GBSA ANALYSIS, MOLECULAR DYNAMICS SIMULATION, ONIOM-QTAIM STUDY, https://purl.org/becyt/ford/1.4Test, https://purl.org/becyt/ford/1Test |
| الوصف: | The main pathogenic event in Alzheimer's disease is believed to be the aggregation of the amyloid β-peptides into toxic aggregates. In a previous work we designed a mimetic peptide possessing a significant aggregation modulating effect by means of a molecular modeling study, using a pentameric model as a molecular target. Considerable experimental evidence indicates that oligomers as small as dimers have been involved in this disease. Therefore, an alternative therapeutic strategy might be to block the oligomerization at a monomeric level. To this end, using an Aβ42 monomeric model, we explored the capacity and mechanism of our mimetic peptides to stabilize the α-helical conformation while preventing the formation of β-sheet structures. Long time molecular dynamics simulations and MM-GBSA analysis were coupled to investigate this issue. In addition, a combined ONIOM-QTAIM analysis was used to identify at a quantum level the most relevant interactions between Aβ42 and this inhibitor. The computational analysis presented here pointed out six important residues of Aβ42 (Lys16, Val36, Gly37, Gly38, Val39 and Val40) that strongly interact with our mimetic peptide, providing clues about the functional groups that might be modified in order to obtain more potent inhibitors. ; Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina ; Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2210-271X |
| العلاقة: | info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2210271X16300159Test; http://hdl.handle.net/11336/55793Test; Barrera Guisasola, Exequiel Ernesto; Gutierrez, Lucas Joel; Salcedo, Rodrigo Emiliano; Garibotto, Francisco Matías; Andujar, Sebastian Antonio; et al.; Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis; Elsevier; Computational and Theoretical Chemistry; 1080; 3-2016; 56-65; CONICET Digital; CONICET |
| الإتاحة: | https://doi.org/10.1016/j.comptc.2016.02.002Test http://hdl.handle.net/11336/55793Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess ; https://creativecommons.org/licenses/by-nc-sa/2.5/arTest/ |
| رقم الانضمام: | edsbas.79567118 |
| قاعدة البيانات: | BASE |
| تدمد: | 2210271X |
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