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Record |
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Author |
Khosravian, N.; Kamaraj, B.; Neyts, E.C.; Bogaerts, A. |
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Title |
Structural modification of P-glycoprotein induced by OH radicals: Insights from atomistic simulations |
Type |
A1 Journal article |
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Year  |
2016 |
Publication |
Scientific reports |
Abbreviated Journal |
Sci Rep-Uk |
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Volume |
6 |
Issue |
6 |
Pages |
19466 |
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Keywords |
A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
This study reports on the possible effects of OH radical impact on the transmembrane domain 6 of P-glycoprotein, TM6, which plays a crucial role in drug binding in human cells. For the first time, we employ molecular dynamics (MD) simulations based on the self-consistent charge density functional tight binding (SCC-DFTB) method to elucidate the potential sites of fragmentation and mutation in this domain upon impact of OH radicals, and to obtain fundamental information about the underlying reaction mechanisms. Furthermore, we apply non-reactive MD simulations to investigate the long-term effect of this mutation, with possible implications for drug binding. Our simulations indicate that the interaction of OH radicals with TM6 might lead to the breaking of C-C and C-N peptide bonds, which eventually cause fragmentation of TM6. Moreover, according to our simulations, the OH radicals can yield mutation in the aromatic ring of phenylalanine in TM6, which in turn affects its structure. As TM6 plays an important role in the binding of a range of cytotoxic drugs with P-glycoprotein, any changes in its structure are likely to affect the response of the tumor cell in chemotherapy. This is crucial for cancer therapies based on reactive oxygen species, such as plasma treatment. |
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Address |
Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium |
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Thesis |
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Publisher |
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Editor |
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Language |
English |
Wos |
000369573900001 |
Publication Date |
2016-02-09 |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2045-2322 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
4.259 |
Times cited |
7 |
Open Access |
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Notes |
The authors acknowledge financial support from the Fund for Scientific Research (FWO) Flanders, grant number G012413N. The calculations were performed in part using the Turing HPC infrastructure of the CalcUA core facility of the Universiteit Antwerpen, a division of the Flemish Supercomputer Center VSC, funded by the Hercules Foundation, the Flemish Government (department EWI) and the Universiteit Antwerpen.” |
Approved |
Most recent IF: 4.259 |
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Call Number |
c:irua:131610 |
Serial |
4031 |
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