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Hydropathic analysis of the free energy differences in anthracycline antibiotic binding to DNA.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cashman, Derek J. Scarsdale, J. Neel Kellogg, Glen Eugene |
| Copyright Year | 2003 |
| Abstract | Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding. The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values. In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of -3.6 +/- 1.1 kcal x mol(-1) (experimental -2.5 +/- 0.5 kcal x mol(-1)) from the groove binding daunosamine sugar. The net energetic contribution of removing the hydroxyl at position C9 is -0.7 +/- 0.7 kcal x mol(-1) (-1.1 +/- 0.5 kcal x mol(-1)). The energetic contribution of the 3' amino group in the daunosamine sugar (when replaced with a hydroxyl group) is -3.7 +/- 1.1 kcal x mol(-1) (-0.7 +/- 0.5 kcal x mol(-1)). We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine. The energetic contribution of the hydroxyl group at C14 is +0.4 +/- 0.6 kcal x mol(-1) (-0.9 +/- 0.5 kcal x mol(-1)), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA. Also, there appears to be considerable conformational uncertainty in this region. This computational procedure calibrates our methodology for future analyses where experimental data are unavailable. |
| Starting Page | 146 |
| Ending Page | 146 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/nar/31/15/10.1093/nar/gkg645/2/gkg645.pdf?Expires=1492945476&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=Y9B1bqyZyYiFKgKvnn5lJnyZryBFVpxVENaXPcD1UeIpPcDMHBWGCRObq1733and0m~EjPQYVdpjjUpZ7UpIMn8nEx-FR6grCautiIy-h1mBTE-1~jTYJj4XYYRC6j6d6U0f-Psz4zLVdFqFORjZ436Ob5uFk0VgG321HzhLKTGhyMV3MQsIERZD1s0VVL2LeeSELgG0xzRoaaCdsfG0d7JD8gKMZ69jy~2W07cVWqnxrB-wbsuloU~Q1JQ3u0Y4ue-tAiwxkp3XqrOKSQOm~v88h9qAvmbuT0cow0adHja9MocpC3qFgCuvEeqLWfLhKGhKFq4qVzl9cyRfFiuSEA__ |
| PubMed reference number | 12888500v1 |
| Volume Number | 31 |
| Issue Number | 15 |
| Journal | Nucleic acids research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Amines Anthracycline Antibiotics Anthracyclines Doxorubicin Ephrin Type-B Receptor 1, human Hydroxyl Radical Oxygen Sugar Alcohol Dehydrogenases Vertebral column carbene cell surface furrow daunosamine free energy hydroxyl group inorganic phosphate invert sugar kilocalorie |
| Content Type | Text |
| Resource Type | Article |
