title: Interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and lisinopril with lipid bilayer membrane: A molecular dynamics simulation study.
abstract: The interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and lisinopril with lipid bilayer membrane dimyristoylphosphatidylcholine (DMPC) has been studied in nine different simulation systems consisting of 128 lipid molecules and appropriate number of water molecules by molecular dynamics method and by utilizing GROMACS software. The influences of PEGylation on the mentioned drugs and the differences in application of two types of spacer molecules on the performance of drugs and DMPC membrane have been evaluated and mass density of the components in the simulation box, mean square displacement (MSD), electrostatic potential, hydrogen bonding, radial distribution function (RDF), area per lipid, order parameter, and angle distribution of the component molecules including drug, DMPC and PEG has been investigated. Furthermore, umbrella sampling analysis indicated that, PEGylation of the drugs made amlodipine to behave more hydrophilic, whereas in case of lisinopril and atenolol, PEGylation made these drugs to behave more hydrophobic. In almost all of the simulated systems, PEGylation increased the diffusion coefficient of the drugs.
authors.affiliation: Department of Nanotechnology, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Yousefpour
authors.affiliation: Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran. Electronic address: hmodares@aut.ac.ir.
authors.forename: Hamid
authors.initials: H
authors.lastname: Modarress
authors.affiliation: Department of Polymer Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Goharpey
authors.affiliation: Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Amjad-Iranagh
mesh_terms: D017311:Amlodipine / Q000031:analogs & derivatives / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D001262:Atenolol / Q000031:analogs & derivatives / Q000737:chemistry*; D004058:Diffusion; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D004735:Energy Transfer; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers; D017706:Lisinopril / Q000031:analogs & derivatives / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D012984:Software; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D008051:Lipid Bilayers; D014867:Water; D017311:Amlodipine; D011092:Polyethylene Glycols; D001262:Atenolol; D017706:Lisinopril; D004134:Dimyristoylphosphatidylcholine
keywords: Anti-hypertensive drug; DMPC bilayer; Molecular dynamics (MD); PEGylation; Umbrella sampling