Molecular dynamics simulation of the sliding of distamycin anticancer drug along DNA: interactions and sequence selectivity

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• 作者：Seifollah Jalili ; Mina Maddah
• 关键词：Molecular dynamics simulation ; Umbrella sampling ; Distamycin ; Minor groove binders ; Sequence selectivity
• 刊名：Journal of the Iranian Chemical Society
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：14
• 期：3
• 页码：531-540
• 全文大小：
• 刊物主题：Analytical Chemistry; Inorganic Chemistry; Physical Chemistry; Biochemistry, general; Organic Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：1735-2428
• 卷排序：14

文摘

Molecular dynamics simulations and umbrella sampling have been used to investigate the sliding of distamycin anticancer drug along the DNA minor groove. The potential energy surface calculated for the sliding of drug shows three minima. The global minimum corresponds to the binding of drug to the AT-rich region, which is the origin of sequence selectivity of distamycin. This selectivity originates from both structural factors and energy contributions. The analysis of energy contributions of binding was performed by the MM–PBSA method. The analysis of hydrogen bonds and van der Waals, electrostatic, and solvation interactions show that structural or steric factors are more important in the selectivity of distamycin than energetic factors. The results of this study can be applied in the design of new derivatives of distamycin anticancer drug with improved properties.