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Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study
[Image: see text] 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...
| Autores principales: | , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2019
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933765/ https://www.ncbi.nlm.nih.gov/pubmed/31891108 http://dx.doi.org/10.1021/acsomega.9b03797 |
| _version_ | 1783483274918625280 |
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| author | Peng, Cheng Atilaw, Yoseph Wang, Jinan Xu, Zhijian Poongavanam, Vasanthanathan Shi, Jiye Kihlberg, Jan Zhu, Weiliang Erdélyi, Máté |
| author_facet | Peng, Cheng Atilaw, Yoseph Wang, Jinan Xu, Zhijian Poongavanam, Vasanthanathan Shi, Jiye Kihlberg, Jan Zhu, Weiliang Erdélyi, Máté |
| author_sort | Peng, Cheng |
| collection | PubMed |
| description | [Image: see text] 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. |
| format | Online Article Text |
| id | pubmed-6933765 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-69337652019-12-30 Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study Peng, Cheng Atilaw, Yoseph Wang, Jinan Xu, Zhijian Poongavanam, Vasanthanathan Shi, Jiye Kihlberg, Jan Zhu, Weiliang Erdélyi, Máté ACS Omega [Image: see text] 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. American Chemical Society 2019-12-16 /pmc/articles/PMC6933765/ /pubmed/31891108 http://dx.doi.org/10.1021/acsomega.9b03797 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
| spellingShingle | Peng, Cheng Atilaw, Yoseph Wang, Jinan Xu, Zhijian Poongavanam, Vasanthanathan Shi, Jiye Kihlberg, Jan Zhu, Weiliang Erdélyi, Máté Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title | Conformation of
the Macrocyclic Drug Lorlatinib in
Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title_full | Conformation of
the Macrocyclic Drug Lorlatinib in
Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title_fullStr | Conformation of
the Macrocyclic Drug Lorlatinib in
Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title_full_unstemmed | Conformation of
the Macrocyclic Drug Lorlatinib in
Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title_short | Conformation of
the Macrocyclic Drug Lorlatinib in
Polar and Nonpolar Environments: A MD Simulation and NMR Study |
| title_sort | conformation of
the macrocyclic drug lorlatinib in
polar and nonpolar environments: a md simulation and nmr study |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933765/ https://www.ncbi.nlm.nih.gov/pubmed/31891108 http://dx.doi.org/10.1021/acsomega.9b03797 |
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