Hydration-Induced Disorder Lowers the Energy Barriers for Methyl Rotation in Drug Molecules.
J Phys Chem Lett
; 11(23): 10256-10261, 2020 Dec 03.
Article
in English
| MEDLINE | ID: covidwho-933650
ABSTRACT
The thermally activated dynamics of methyl groups are important for biochemical activity as they allow for a more efficient sampling of the energy landscape. Here, we compare methyl rotations in the dry and variously hydrated states of three primary drugs under consideration to treat the recent coronavirus disease (COVID-19), namely, hydroxychloroquine and its sulfate, dexamethasone and its sodium diphosphate, and remdesivir. We find that the main driving force behind the considerable reduction in the activation energy for methyl rotations in the hydrated state is the hydration-induced disorder in the methyl group local environments. Furthermore, the activation energy for methyl rotations in the hydration-induced disordered state is much lower than that in an isolated drug molecule, indicating that neither isolated molecules nor periodic crystalline structures can be used to analyze the potential landscape governing the side group dynamics in drug molecules. Instead, only the explicitly considered disordered structures can provide insight.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
Type of study:
Experimental Studies
/
Randomized controlled trials
Language:
English
Journal:
J Phys Chem Lett
Year:
2020
Document Type:
Article
Affiliation country:
Acs.jpclett.0c02642
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