Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study.
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ABSTRACT:
SUBMITTER: Peng C
PROVIDER: S-EPMC6933765 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study.
Peng Cheng C Atilaw Yoseph Y Wang Jinan J Xu Zhijian Z Poongavanam Vasanthanathan V Shi Jiye J Kihlberg Jan J Zhu Weiliang W Erdélyi Máté M
ACS omega 20191216 26
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 cr ...[more]
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