Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study
Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study
复制标题
大环药物 Lorlatinib 在极性和非极性环境中的构象：MD 模拟和 NMR 研究
作者：
Cheng Peng;Yoseph Atilaw;Jinan Wang;Zhijian Xu;Vasanthanathan Poongavanam;Jiye Shi;J. Kihlberg;Weiliang Zhu;M. Erdélyi
副本交换分子动力学（REMD）模拟证明，很容易预测的大环药物劳拉替尼的构象，通过溶液NMR研究验证。在水溶液中，劳拉替尼采用与其目标结合结构相同的构象异构体。该构象异构体通过与溶剂的广泛氢键网络而稳定。在氯仿中，劳拉替尼占据两种构象，第二种构象极性较低，这可能有助于劳拉替尼穿过细胞膜的能力。
The replica exchange molecular dynamics (REMD) simulation is demonstrated to readily predict the conformations of the macrocyclic drug lorlatinib, as validated by solution NMR studies. In aqueous solution, lorlatinib adopts a conformer identical to its target bound structure. This conformer is stabilized by an extensive hydrogen bond network to the solvents. In chloroform, lorlatinib populates two conformers with the second one being less polar, which may contribute to lorlatinib’s ability to cross cell membranes.
影响因子：
--
作者：
Wang W;Groves MR;Dömling A
通讯作者：
Dömling A
影响因子：
5.5
作者：
Ardita Shkurti;I. D. Styliari;Vivek Balasubramanian;I. Bethune;Conrado Pedebos;S. Jha;C. Laughton
通讯作者：
Ardita Shkurti;I. D. Styliari;Vivek Balasubramanian;I. Bethune;Conrado Pedebos;S. Jha;C. Laughton
影响因子：
15
作者：
Rezai, T;Yu, B;Lokey, RS
通讯作者：
Lokey, RS