Thermodynamic Dissection of the Intercalation Binding Process of Doxorubicin to dsDNA with Implications of Ionic and Solvent Effects
| Autor: | Rudolf Podgornik, Lokendra Poudel, Bahaa Jawad, Wai-Yim Ching |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Intercalation (chemistry)
Ionic bonding Dissection (medical) 010402 general chemistry 01 natural sciences Molecular dynamics symbols.namesake 0103 physical sciences polycyclic compounds Materials Chemistry medicine Doxorubicin Physical and Theoretical Chemistry skin and connective tissue diseases Ions 010304 chemical physics Chemistry Dissection organic chemicals technology industry and agriculture DNA medicine.disease 0104 chemical sciences Surfaces Coatings and Films carbohydrates (lipids) Microsecond Solvents symbols Biophysics Thermodynamics van der Waals force Solvent effects medicine.drug |
| Zdroj: | The Journal of Physical Chemistry B. 124:7803-7818 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.0c05840 |
| Popis: | Doxorubicin (DOX) is a cancer drug that binds to dsDNA through intercalation. A comprehensive microsecond timescale molecular dynamics study is performed for DOX with 16 tetradecamer dsDNA sequences in explicit aqueous solvent, in order to investigate the intercalation process at both binding stages (conformational change and insertion binding stages). The molecular mechanics generalized Born surface area (MM-GBSA) method is adapted to quantify and break down the binding free energy (BFE) into its thermodynamic components, for a variety of different solution conditions as well as different DNA sequences. Our results show that the van der Waals interaction provides the largest contribution to the BFE at each stage of binding. The sequence selectivity depends mainly on the base pairs located downstream from the DOX intercalation site, with a preference for (AT) |
| Databáze: | OpenAIRE |
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