Investigation of benzodiazepines (BZDs) in a DPPC lipid bilayer: Insights from molecular dynamics simulation and DFT calculations
| Autor: | Mokhtar Ganjali Koli, Khaled Azizi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
1
2-Dipalmitoylphosphatidylcholine Lipid Bilayers Static Electricity Molecular Dynamics Simulation 01 natural sciences Diffusion Benzodiazepines 03 medical and health sciences chemistry.chemical_compound Molecular dynamics 0103 physical sciences Materials Chemistry Physical and Theoretical Chemistry Potential of mean force Lipid bilayer Density Functional Theory Spectroscopy 030304 developmental biology 0303 health sciences 010304 chemical physics Bilayer Penetration (firestop) Computer Graphics and Computer-Aided Design Membrane chemistry Chemical physics Dipalmitoylphosphatidylcholine Density functional theory |
| Zdroj: | Journal of Molecular Graphics and Modelling. 90:171-179 |
| ISSN: | 1093-3263 |
| DOI: | 10.1016/j.jmgm.2019.04.012 |
| Popis: | Toxicity is an essential parameter for drug development process and drug design. In this context, the effects of concentration of two Benzodiazepine drugs (diazepam, clonazepam) on fully hydrated dipalmitoylphosphatidylcholine (DPPC) has been studied at 323 K using molecular dynamics simulations. Various properties of bilayer such as membrane area per lipid, mass density distributions, order parameters, radial distribution functions, lateral diffusion, and electrostatic potential have been examined at three different concentrations of each drug. The location of drugs in the membrane are estimated by free energy profiles and to evaluate the results at a more detailed theoretical level, density functional theory (DFT) calculations have been carried out. It was revealed that penetration into the bilayer for diazepam is more favorable than clonazepam. On the other hand, within the fatty acid tail area both drugs are located in the middle of membrane at ∼0.75–1.5 nm from center of bilayer. |
| Databáze: | OpenAIRE |
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