Estimating localization of various statins within a POPC bilayer
Jacob Olondo Kuba1, Yalun Yu2, Jeffery B Klauda3
1Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, 20742, USA.
Chemistry and Physics of Lipids
|March 7, 2021
Summary
Statins exhibit varied membrane localization, influencing heart disease treatment. This study used molecular dynamics simulations to reveal how different statins interact within cell membranes, impacting their pleiotropic effects.
Area of Science:
- Biochemistry
- Computational Biology
- Pharmacology
Background:
- Statins are widely prescribed for heart disease.
- Beyond cholesterol reduction, statins possess beneficial pleiotropic effects.
- These effects may be linked to statin localization within cell membranes.
Purpose of the Study:
- To investigate the membrane localization of four statins: atorvastatin, cerivastatin, lovastatin, and pravastatin.
- To determine how statin localization affects membrane properties such as acyl chain order parameters, surface area per lipid, and bilayer thickness.
- To correlate statin hydrophilicity with their membrane interactions and potential pleiotropic effects.
Main Methods:
- Utilized molecular dynamics (MD) simulations.
- Employed the CHARMM36 all-atom force field.
- Simulated statins within a 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) lipid bilayer over 500 nanoseconds.
Main Results:
- Lovastatin localized deepest, interacting with the hydrophobic core.
- Cerivastatin and pravastatin showed progressively shallower localization, interacting with headgroups and the bilayer/solvent interface.
- Atorvastatin exhibited inconsistent binding due to self-aggregation.
- Statins induced modest alterations in membrane acyl chain order, surface area per lipid, and thickness.
Conclusions:
- Statin membrane localization correlates with their hydrophilicity.
- Differential localization suggests varied interactions with membrane components.
- These distinct interactions may underlie the diverse pleiotropic effects observed among different statins.
- Findings offer insights into statin-membrane interactions in a simplified model.
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