Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations
| العنوان: | Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations |
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| المؤلفون: | Sowmya Indrakumar, Sujata Mahapatra, Alina Kulakova, Werner Streicher, Günther H.J. Peters, Pernille Harris, Pernille Sønderby Tuelung |
| المصدر: | Scientific reports 10(1), 10089 (2020). doi:10.1038/s41598-020-67002-9 Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Kulakova, A, Indrakumar, S, Sønderby Tuelung, P, Mahapatra, S, Streicher, W W, Peters, G H J & Harris, P 2020, ' Albumin-neprilysin fusion protein : understanding stability using small angle X-ray scattering and molecular dynamic simulations ', Scientific Reports, vol. 10, no. 1, 10089 . https://doi.org/10.1038/s41598-020-67002-9 Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Conformation, lcsh:Medicine, Serum Albumin, Human, Molecular Dynamics Simulation, Protein Engineering, 010402 general chemistry, 01 natural sciences, Article, 03 medical and health sciences, Molecular dynamics, Protein structure, X-Ray Diffraction, Albumins, Scattering, Small Angle, lcsh:Science, Multidisciplinary, Protein Stability, Scattering, Chemistry, Small-angle X-ray scattering, lcsh:R, High-throughput screening, SAXS, Hydrogen-Ion Concentration, Fusion power, Fusion protein, 0104 chemical sciences, 030104 developmental biology, Intramolecular force, Volume fraction, Biophysics, Neprilysin, lcsh:Q, Molecular modelling, ddc:600 |
| الوصف: | Scientific reports 10(1), 10089 (2020). doi:10.1038/s41598-020-67002-9 Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0. Published by Macmillan Publishers Limited, part of Springer Nature, [London] |
| وصف الملف: | application/pdf |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::955977592cb56d1e5059fcdf00a7d507 https://doi.org/10.1038/s41598-020-67002-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....955977592cb56d1e5059fcdf00a7d507 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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