title: Benchmarking of Force Fields for Molecule-Membrane Interactions.
abstract: Studies of drug-membrane interactions witness an ever-growing interest, as penetration, accumulation, and positioning of drugs play a crucial role in drug delivery and metabolism in human body. Molecular dynamics simulations complement nicely experimental measurements and provide us with new insight into drug-membrane interactions; however, the quality of the theoretical data dramatically depends on the quality of the force field used. We calculated the free energy profiles of 11 molecules through a model dimyristoylphosphatidylcholine (DMPC) membrane bilayer using five force fields, namely Berger, Slipids, CHARMM36, GAFFlipids, and GROMOS 43A1-S3. For the sake of comparison, we also employed the semicontinuous tool COSMOmic. High correlation was observed between theoretical and experimental partition coefficients (log K). Partition coefficients calculated by all-atomic force fields (Slipids, CHARMM36, and GAFFlipids) and COSMOmic differed by less than 0.75 log units from the experiment and Slipids emerged as the best performing force field. This work provides the following recommendations (i) for a global, systematic and high throughput thermodynamic evaluations (e.g., log K) of drugs COSMOmic is a tool of choice due to low computational costs; (ii) for studies of the hydrophilic molecules CHARMM36 should be considered; and (iii) for studies of more complex systems, taking into account all pros and cons, Slipids is the force field of choice.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc , tř. 17 Listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Paloncýová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc , tř. 17 Listopadu 12, 771 46 Olomouc, Czech Republic.|LCSN EA1069, Faculté de Pharmacie, Université de Limoges , 2 Rue de Docteur Marcland, 87025 Limoges Cedex, France.
authors.forename: Gabin
authors.initials: G
authors.lastname: Fabre
authors.affiliation: Corporate Modeling and Simulation, Procter and Gamble, 8611 Beckett Road, West Chester, Ohio 45069, United States.
authors.forename: Russell H
authors.initials: RH
authors.lastname: DeVane
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc , tř. 17 Listopadu 12, 771 46 Olomouc, Czech Republic.|INSERM UMR-S850, Faculté de Pharmacie, Université de Limoges , 2 Rue du Docteur Marcland, 87025 Limoges Cedex, France.|Laboratoire de Chimie des Matériaux Nouveaux, Université de Mons , Place du Parc 20, B-7000 Mons, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc , tř. 17 Listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Berka
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc , tř. 17 Listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka