PDF(Pubmed)
Abstract：
Berubicin, a chemotherapy medication belonging to the class of anthracyclines, is simulated in double-stranded DNA sequences and cyclodextrins in an aqueous environment via full-atom molecular dynamics simulations on the time scale of microseconds. The drug is studied in both the neutral and protonated states so as to better comprehend the role of its charge in the formed complexes. The noncovalent berubicin-DNA and berubicin-cyclodextrin complexes are investigated in detail, paying special attention to their thermodynamic description by employing the double decoupling method, the solvent balance method, the weighted solvent accessible surface model, and the linear interaction energy method. A novel approach for extracting the desolvation thermodynamics of the binding process is also presented. Both the binding and desolvation Gibbs energies are decomposed into entropic and enthalpic contributions so as to elucidate the nature of complexation and its driving forces. Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out.
摘要：
Berubicin,属于蒽环类的化疗药物，通过在微秒的时间尺度上的全原子分子动力学模拟，在水性环境中的双链DNA序列和环糊精中进行模拟。在中性和质子化状态下研究该药物，以便更好地理解其电荷在形成的复合物中的作用。详细研究了非共价的小柔比星-DNA和小柔比星-环糊精复合物，通过采用双重解耦方法特别注意它们的热力学描述，溶剂平衡法,加权溶剂可及表面模型，和线性相互作用能方法。还提出了一种用于提取结合过程的去溶剂化热力学的新方法。结合和去溶剂化吉布斯能都分解为熵和焓贡献，以阐明络合的性质及其驱动力。所有配合物的选定结构和几何性质，都是稳定的，被分析。所考虑的两种环糊精都广泛用于药物递送目的，并对它们与小柔比星的结合状态进行了比较研究。
