Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs.
Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs.
复制标题
应用于单功能和双功能铂抗癌药物的水自由能分布的蓝月系综模拟。
DOI：
10.1002/jcc.26367
复制
发表时间：
2020
影响因子：
3
通讯作者：
Hirakawa T
中科院分区：
文献类型：
--
作者：
Hirakawa T
用热力学积分法计算了中性顺铂和阳离子单官能衍生物三氨基氯铂(II)和顺二胺(吡啶)氯铂(II)的水合自由能分布，其中温度和溶剂用基于密度泛函理论的正则分子动力学(DFT-MD)计算。对于所有的体系，都观察到了金属中心作为氢键的接受者的“逆水化”。这促使在反应坐标的定义中考虑反键的溶剂分子，该反应坐标是启动受约束的DFT-MD轨迹所需的。我们发现，这些铂类抗癌药物的自由活化热几乎没有差别，因此它们在水介质中的作用可能是相同的。详细分析了正方形平面络合物的微溶剂化结构，以及水合机理的关键步骤。
Aquation free energy profiles of neutral cisplatin and cationic monofunctional derivatives, including triaminochloroplatinum(II) and cis‐diammine(pyridine)chloroplatinum(II), were computed using state of the art thermodynamic integration, for which temperature and solvent were accounted for explicitly using density functional theory‐based canonical molecular dynamics (DFT‐MD). For all the systems, the “inverse‐hydration” where the metal center acts as an acceptor of hydrogen bond has been observed. This has motivated to consider the inversely bonded solvent molecule in the definition of the reaction coordinate required to initiate the constrained DFT‐MD trajectories. We found that there exists little difference in free enthalpies of activation, such that these platinum‐based anticancer drugs are likely to behave the same way in aqueous media. Detailed analysis of the microsolvation structure of the square‐planar complexes, along with the key steps of the aquation mechanism, is discussed.