Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16, Prague 2, Czech Republic.
NEQC: Núcleo de Estudos em Química Computacional, Departamento de Química-ICE, Universidade Federal e Juiz de Fora, Juiz de Fora, MG, 36036-330, Brazil.
J Biol Inorg Chem. 2018 May;23(3):363-376. doi: 10.1007/s00775-018-1536-x. Epub 2018 Feb 8.
Interaction of cisplatin in activated diaqua-form with His-Met dipeptide is explored using DFT approach with PCM model. First the conformation space of the dipeptide is explored to find the most stable structure (labeled 0683). Several functionals with double-zeta basis set are used for optimization and obtained order of conformers is confirmed by the CCSD(T) single-point calculations. Supermolecular model is used to determine reaction coordinate for the replacement of aqua ligands consequently by N-site of histidine and S-site of methionine and reversely. Despite the monoadduct of Pt-S(Met) is thermodynamically less stable this reaction passes substantially faster (by several orders of magnitude) than coordination of cisplatin to histidine. The consequent chelate formation occurs relatively fast with energy release up to 12 kcal mol.
采用 DFT 方法结合 PCM 模型研究了顺铂在激活的二水合形式中与 His-Met 二肽的相互作用。首先，探索二肽的构象空间，找到最稳定的结构（标记为 0683）。使用双 ζ 基组的几种泛函进行优化，并通过 CCSD(T)单点计算确认构象的顺序。超分子模型用于确定取代水合配体的反应坐标，从而由组氨酸的 N 位和蛋氨酸的 S 位取代，反之亦然。尽管 Pt-S(Met)的单加合物热力学上不太稳定，但该反应的速度（快几个数量级）明显快于顺铂与组氨酸的配位。随后的螯合形成发生得相对较快，释放能量高达 12 kcal/mol。
