{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:17:32Z","timestamp":1770081452001,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}]},{"name":"European Regional Development Fund","award":["UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDP\/00313\/2020"]}]},{"name":"European Regional Development Fund","award":["CENTRO-04-3559-FSE-000162"],"award-info":[{"award-number":["CENTRO-04-3559-FSE-000162"]}]},{"DOI":"10.13039\/501100001871","name":"Portuguese funds via FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese funds via FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDP\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese funds via FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CENTRO-04-3559-FSE-000162"],"award-info":[{"award-number":["CENTRO-04-3559-FSE-000162"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Social Fund (ESF)","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}]},{"name":"European Social Fund (ESF)","award":["UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDP\/00313\/2020"]}]},{"name":"European Social Fund (ESF)","award":["CENTRO-04-3559-FSE-000162"],"award-info":[{"award-number":["CENTRO-04-3559-FSE-000162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Permeation through biomembranes is ubiquitous for drugs to reach their active sites. Asymmetry of the cell plasma membrane (PM) has been described as having an important role in this process. Here we describe the interaction of a homologous series of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled amphiphiles (NBD-Cn, n = 4 to 16) with lipid bilayers of different compositions (1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol (1:1) and palmitoylated sphingomyelin (SpM):cholesterol (6:4)), including an asymmetric bilayer. Both unrestrained and umbrella sampling (US) simulations (at varying distances to the bilayer center) were carried out. The free energy profile of NBD-Cn at different depths in the membrane was obtained from the US simulations. The behavior of the amphiphiles during the permeation process was described regarding their orientation, chain elongation, and H-bonding to lipid and water molecules. Permeability coefficients were also calculated for the different amphiphiles of the series, using the inhomogeneous solubility-diffusion model (ISDM). Quantitative agreement with values obtained from kinetic modeling of the permeation process could not be obtained. However, for the longer, and more hydrophobic amphiphiles, the variation trend along the homologous series was qualitatively better matched by the ISDM when the equilibrium location of each amphiphile was taken as reference (\u0394G = 0), compared to the usual choice of bulk water.<\/jats:p>","DOI":"10.3390\/membranes13060551","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T02:30:06Z","timestamp":1684981806000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Permeation of a Homologous Series of NBD-Labeled Fatty Amines through Lipid Bilayers: A Molecular Dynamics Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-4307","authenticated-orcid":false,"given":"Hugo A. L.","family":"Filipe","sequence":"first","affiliation":[{"name":"Coimbra Chemistry Center, Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"CPIRN-IPG\u2014Center of Potential and Innovation of Natural Resources, Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-2312","authenticated-orcid":false,"given":"Lu\u00eds M. S.","family":"Loura","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Center, Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-9905","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Moreno","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Center, Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra, 3004-535 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.drudis.2011.05.010","article-title":"Pharmaceutical drug transport: The issues and the implications that it is essentially carrier-mediated only","volume":"16","author":"Kell","year":"2011","journal-title":"Drug. Discov. Today"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrd3187","article-title":"Coexistence of passive and carrier-mediated processes in drug transport","volume":"9","author":"Sugano","year":"2010","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1021\/mp400713v","article-title":"Passive Lipoidal Diffusion and Carrier-Mediated Cell Uptake Are Both Important Mechanisms of Membrane Permeation in Drug Disposition","volume":"11","author":"Smith","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1529\/biophysj.104.054007","article-title":"Kinetics and thermodynamics of association of a fluorescent lysophospholipid derivative with lipid bilayers in liquid-ordered and liquid-disordered phases","volume":"88","author":"Sampaio","year":"2005","journal-title":"Biophys. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00232-017-0009-4","article-title":"Effect of Acyl Chain Length on the Rate of Phospholipid Flip-Flop and Intermembrane Transfer","volume":"251","author":"Vaz","year":"2018","journal-title":"J. Membr. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1529\/biophysj.107.112847","article-title":"Kinetics and thermodynamics of the association of dehydroergosterol with lipid bilayer membranes","volume":"93","author":"Estronca","year":"2007","journal-title":"Biophys. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10098","DOI":"10.1021\/jp203429s","article-title":"Chain-Length Dependence of Insertion, Desorption, and Translocation of a Homologous Series of 7-Nitrobenz-2-oxa-1,3-diazol-4-yl-Labeled Aliphatic Amines in Membranes","volume":"115","author":"Cardoso","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1021\/ja209917q","article-title":"Kinetics and Thermodynamics of Chlorpromazine Interaction with Lipid Bilayers: Effect of Charge and Cholesterol","volume":"134","author":"Martins","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1529\/biophysj.106.082115","article-title":"Translocation of phospholipids and dithionite permeability in liquid-ordered and liquid-disordered membranes","volume":"91","author":"Moreno","year":"2006","journal-title":"Biophys. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1529\/biophysj.104.040576","article-title":"Kinetics and thermodynamics of association of a phospholipid derivative with lipid bilayers in liquid-disordered and liquid-ordered phases","volume":"87","author":"Abreu","year":"2004","journal-title":"Biophys. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/mp500437e","article-title":"Beyond Overton\u2019s Rule: Quantitative Modeling of Passive Permeation through Tight Cell Monolayers","volume":"11","author":"Filipe","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_12","unstructured":"Deamer, D.W., Kleinzeller, A., and Fambrough, D.M. (1999). Current Topics in Membranes, Academic Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1021\/jp4112052","article-title":"Amphiphilic Drug-Like Molecules Accumulate in a Membrane below the Head Group Region","volume":"118","author":"DeVane","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11248","DOI":"10.1021\/jp204488j","article-title":"Membrane Position of Ibuprofen Agrees with Suggested Access Path Entrance to Cytochrome P450 2C9 Active Site","volume":"115","author":"Berka","year":"2011","journal-title":"J. Phys. Chem. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1021\/acs.jpcb.9b10092","article-title":"Menthol Binding to the Human \u03b14\u03b22 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane","volume":"124","author":"Shahoei","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1021\/acschemneuro.9b00656","article-title":"Membrane-Dependent Binding and Entry Mechanism of Dopamine into Its Receptor","volume":"11","author":"Lolicato","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Moreno, M.J., Filipe, H.A.L., Cunha, S.V.P., Ramos, C.V., Martins, P.A.T., Abel, B., Loura, L.M.S., and Ambudkar, S.V. (2023). Interaction of a Homologous Series of Amphiphiles with P-glycoprotein in a Membrane Environment\u2014Contributions of Polar and Non-Polar Interactions. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010174"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moreno, M.J., and Salvador, A. (2023). Ligand\u2019s Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins. Molecules, 28.","DOI":"10.3390\/molecules28073136"},{"key":"ref_19","first-page":"1309","article-title":"Positioning of Antioxidant Quercetin and Its Metabolites in Lipid Bilayer Membranes: Implication for Their Lipid-Peroxidation Inhibition","volume":"116","author":"Berka","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.freeradbiomed.2017.12.002","article-title":"Differential targeting of membrane lipid domains by caffeic acid and its ester derivatives","volume":"115","author":"Filipe","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1039\/C8CC09656B","article-title":"Quercetin dual interaction at the membrane level","volume":"55","author":"Sousa","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: Where they are and how they behave","volume":"9","author":"Voelker","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Moreno, M.J., Teles Martins, P.A., Bernardino, E.F., Abel, B., and Ambudkar, S.V. (2021). Characterization of the Lipidome and Biophysical Properties of Membranes from High Five Insect Cells Expressing Mouse P-Glycoprotein. Biomolecules, 11.","DOI":"10.20944\/preprints202102.0204.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev.bi.48.070179.000403","article-title":"Lipid Asymmetry in Membranes","volume":"48","year":"1979","journal-title":"Annu. Rev. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/0-306-47931-1_3","article-title":"Plasma Membrane Phospholipid Asymmetry","volume":"Volume 36","author":"Quinn","year":"2002","journal-title":"Phospholipid Metabolism in Apoptosis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13342","DOI":"10.1021\/jp108166k","article-title":"Cholesterol Flip-Flop: Insights from Free Energy Simulation Studies","volume":"114","author":"Jo","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1194\/jlr.M022491","article-title":"Molecular simulation of rapid translocation of cholesterol, diacylglycerol, and ceramide in model raft and nonraft membranes","volume":"53","author":"Bennett","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.bpj.2011.10.059","article-title":"How Slow Is the Transbilayer Diffusion (Flip-Flop) of Cholesterol?","volume":"102","author":"Steck","year":"2012","journal-title":"Biophys. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.1021\/acs.jctc.8b00150","article-title":"Quantitative Assessment of Methods Used to Obtain Rate Constants from Molecular Dynamics Simulations\u2014Translocation of Cholesterol across Lipid Bilayers","volume":"14","author":"Filipe","year":"2018","journal-title":"J. Chem. Theory Comput."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12028","DOI":"10.1021\/bi034931+","article-title":"Interaction of Cholesterol with a Docosahexaenoic Acid-Containing Phosphatidylethanolamine:\u2009 Trigger for Microdomain\/Raft Formation?","volume":"42","author":"Shaikh","year":"2003","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6950","DOI":"10.1021\/bi400862q","article-title":"Stability and Stoichiometry of Bilayer Phospholipid\u2013Cholesterol Complexes: Relationship to Cellular Sterol Distribution and Homeostasis","volume":"52","author":"Lange","year":"2013","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0022-2275(20)38890-8","article-title":"Composition of phospholipids and of phospholipid fatty acids and aldehydes in human red cells","volume":"8","author":"Dodge","year":"1967","journal-title":"J. Lipid Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1126\/science.402030","article-title":"Membrane asymmetry","volume":"195","author":"Rothman","year":"1977","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev.bb.21.060192.002221","article-title":"Protein involvement in transmembrane lipid asymmetry","volume":"21","author":"Devaux","year":"1992","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0022-2275(20)38181-5","article-title":"Decreased Erythrocyte membrane fluidity and altered lipid composition in human liver disease","volume":"23","author":"Owen","year":"1982","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.bbalip.2008.07.008","article-title":"Mass spectrometric analysis of lipid species of human circulating blood cells","volume":"1781","author":"Leidl","year":"2008","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1161\/HYPERTENSIONAHA.109.137471","article-title":"Mediterranean-Style Diet Effect on the Structural Properties of the Erythrocyte Cell Membrane of Hypertensive Patients: The Prevencion con Dieta Mediterranea Study","volume":"54","author":"Perona","year":"2009","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1073\/pnas.73.1.173","article-title":"Analysis of membrane halves: Cholesterol","volume":"73","author":"Fisher","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0304-4157(85)90011-5","article-title":"Cholesterol and the cell membrane","volume":"822","author":"Yeagle","year":"1985","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Rev. Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1038\/s41596-018-0033-6","article-title":"Preparation of asymmetric phospholipid vesicles for use as cell membrane models","volume":"13","author":"Doktorova","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.bpj.2019.10.043","article-title":"Stairway to Asymmetry: Five Steps to Lipid-Asymmetric Proteoliposomes","volume":"118","author":"Markones","year":"2020","journal-title":"Biophys. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1529\/biophysj.106.096214","article-title":"Molecular Dynamics Simulations of SOPS and Sphingomyelin Bilayers Containing Cholesterol","volume":"92","author":"Bhide","year":"2007","journal-title":"Biophys. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1021\/ja070949m","article-title":"Lipid Transmembrane Asymmetry and Intrinsic Membrane Potential:\u2009 Two Sides of the Same Coin","volume":"129","author":"Gurtovenko","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1021\/jp8001993","article-title":"Membrane Potential and Electrostatics of Phospholipid Bilayers with Asymmetric Transmembrane Distribution of Anionic Lipids","volume":"112","author":"Gurtovenko","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3390\/membranes5020180","article-title":"Asymmetric Lipid Membranes: Towards More Realistic Model Systems","volume":"5","author":"Marquardt","year":"2015","journal-title":"Membranes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2113297119","DOI":"10.1073\/pnas.2113297119","article-title":"Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins","volume":"119","author":"Neale","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0021-9991(77)90121-8","article-title":"Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling","volume":"23","author":"Torrie","year":"1977","journal-title":"J. Comput. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/wcms.66","article-title":"Umbrella sampling","volume":"1","year":"2011","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1021\/ct301005b","article-title":"Accelerating Convergence in Molecular Dynamics Simulations of Solutes in Lipid Membranes by Conducting a Random Walk along the Bilayer Normal","volume":"9","author":"Neale","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1021\/jacs.6b11215","article-title":"Structure\u2013Kinetic Relationships of Passive Membrane Permeation from Multiscale Modeling","volume":"139","author":"Dickson","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"baz078","DOI":"10.1093\/database\/baz078","article-title":"MolMeDB: Molecules on Membranes Database","volume":"2019","author":"Bazgier","year":"2019","journal-title":"Database"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"184120","DOI":"10.1016\/j.bbamem.2023.184120","article-title":"MemCross: Accelerated Weight Histogram method to assess membrane permeability","volume":"1865","author":"Benmameri","year":"2023","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S1063-5823(08)00008-2","article-title":"Chapter 8 Interactions between Small Molecules and Lipid Bilayers","volume":"Volume 60","author":"Scott","year":"2008","journal-title":"Current Topics in Membranes"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1021\/jp035260s","article-title":"Permeation of small molecules through a lipid bilayer: A computer simulation study","volume":"108","author":"Bemporad","year":"2004","journal-title":"J. Phys. Chem. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1021\/ct2009208","article-title":"Convergence of Free Energy Profile of Coumarin in Lipid Bilayer","volume":"8","author":"Berka","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"16337","DOI":"10.1021\/jp105163k","article-title":"Chain Length Effect on the Binding of Amphiphiles to Serum Albumin and to POPC Bilayers","volume":"114","author":"Cardoso","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10109","DOI":"10.1021\/jp203532c","article-title":"Interaction of 7-Nitrobenz-2-oxa-1,3-diazol-4-yl-Labeled Fatty Amines with 1-Palmitoyl, 2-Oleoyl-sn-glycero-3-phosphocholine Bilayers: A Molecular Dynamics Study","volume":"115","author":"Filipe","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3572","DOI":"10.1021\/jp501622d","article-title":"How To Tackle the Issues in Free Energy Simulations of Long Amphiphiles Interacting with Lipid Membranes: Convergence and Local Membrane Deformations","volume":"118","author":"Filipe","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27534","DOI":"10.1039\/C5CP04191K","article-title":"Interaction of NBD-labelled fatty amines with liquid-ordered membranes: A combined molecular dynamics simulation and fluorescence spectroscopy study","volume":"17","author":"Filipe","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","author":"Pronk","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1529\/biophysj.104.052399","article-title":"H-2-NMR study and molecular dynamics simulation of the location, alignment, and mobility of pyrene in POPC bilayers","volume":"88","author":"Hoff","year":"2005","journal-title":"Biophys. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/S0006-3495(97)78845-3","article-title":"Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature","volume":"72","author":"Berger","year":"1997","journal-title":"Biophys. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105103","DOI":"10.1063\/1.2976443","article-title":"Influence of cis double-bond parametrization on lipid membrane properties: How seemingly insignificant details in force-field change even qualitative trends","volume":"129","author":"Karttunen","year":"2008","journal-title":"J. Chem. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1529\/biophysj.104.048702","article-title":"Structure and Dynamics of Sphingomyelin Bilayer: Insight Gained through Systematic Comparison to Phosphatidylcholine","volume":"87","author":"Vattulainen","year":"2004","journal-title":"Biophys. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00232-010-9296-8","article-title":"Lipidbook: A Public Repository for Force-Field Parameters Used in Membrane Simulations","volume":"236","author":"Stansfeld","year":"2010","journal-title":"J. Membr. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0005-2736(01)00270-X","article-title":"Molecular dynamics simulations of stratum corneum lipid models: Fatty acids and cholesterol","volume":"1511","author":"Brandt","year":"2001","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1021\/ct500419b","article-title":"Benchmarking of Force Fields for Molecule\u2013Membrane Interactions","volume":"10","author":"Fabre","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/978-94-015-7658-1_21","article-title":"Interaction Models for Water in Relation to Protein Hydration","volume":"Volume 14","author":"Pullman","year":"1981","journal-title":"Intermolecular Forces"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models","volume":"13","author":"Miyamoto","year":"1992","journal-title":"J. Comput. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/S0006-3495(03)75025-5","article-title":"Molecular dynamics simulations of phospholipid bilayers with cholesterol","volume":"84","author":"Hofsass","year":"2003","journal-title":"Biophys. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1017\/S0033583500002948","article-title":"Deuterium magnetic resonance: Theory and application to lipid membranes","volume":"10","author":"Seelig","year":"1977","journal-title":"Q. Rev. Biophys."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0010-4655(95)00053-I","article-title":"The calculation of the potential of mean force using computer simulations","volume":"91","author":"Roux","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1021\/ct100494z","article-title":"g_wham\u2014A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates","volume":"6","author":"Hub","year":"2010","journal-title":"J. Chem. Theory Comput."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1021\/j100066a040","article-title":"Simulation of water transport through a lipid membrane","volume":"98","author":"Marrink","year":"1994","journal-title":"J. Phys. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"183157","DOI":"10.1016\/j.bbamem.2019.183157","article-title":"Effect of dipole moment on amphiphile solubility and partition into liquid ordered and liquid disordered phases in lipid bilayers","volume":"1862","author":"Cardoso","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12714","DOI":"10.1021\/ja903529f","article-title":"Molecular View of Cholesterol Flip-Flop and Chemical Potential in Different Membrane Environments","volume":"131","author":"Bennett","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1021\/ja808541r","article-title":"Thermodynamic Analysis of the Effect of Cholesterol on Dipalmitoylphosphatidylcholine Lipid Membranes","volume":"131","author":"Bennett","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1021\/bi0520840","article-title":"Cholesterol Hydroxyl Group Is Found To Reside in the Center of a Polyunsaturated Lipid Membrane","volume":"45","author":"Harroun","year":"2006","journal-title":"Biochemistry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.1021\/bi800123b","article-title":"Cholesterol Is Found To Reside in the Center of a Polyunsaturated Lipid Membrane","volume":"47","author":"Harroun","year":"2008","journal-title":"Biochemistry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0005-2736(88)90155-1","article-title":"Transbilayer diffusion of phospholipids: Dependence on headgroup structure and acyl chain length","volume":"938","author":"Homan","year":"1988","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Neves, M.C., Filipe, H.A.L., Reis, R.L., Prates Ramalho, J.P., Coreta-Gomes, F., Moreno, M.J., and Loura, L.M.S. (2019). Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00393"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9097","DOI":"10.1021\/acs.langmuir.5b01810","article-title":"Interaction of Bile Salts with Model Membranes Mimicking the Gastrointestinal Epithelium: A Study by Isothermal Titration Calorimetry","volume":"31","author":"Martins","year":"2015","journal-title":"Langmuir"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"13942","DOI":"10.1021\/la503289v","article-title":"Rationalization of Reduced Penetration of Drugs through Ceramide Gel Phase Membrane","volume":"30","author":"DeVane","year":"2014","journal-title":"Langmuir"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0031-8914(40)90098-2","article-title":"Brownian motion in a field of force and the diffusion model of chemical reactions","volume":"7","author":"Kramers","year":"1940","journal-title":"Physica"},{"key":"ref_90","unstructured":"Aniansson, E.A.G. (1975). Chemical and Biological Applications of Relaxation Spectrometry, Springer."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.1074\/jbc.M806077200","article-title":"Preparation and Properties of Asymmetric Vesicles That Mimic Cell Membranes*","volume":"284","author":"Cheng","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bpj.2018.07.011","article-title":"Lipid Structure and Composition Control Consequences of Interleaflet Coupling in Asymmetric Vesicles","volume":"115","author":"Wang","year":"2018","journal-title":"Biophys. J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1021\/acs.langmuir.7b03189","article-title":"Engineering Asymmetric Lipid Vesicles: Accurate and Convenient Control of the Outer Leaflet Lipid Composition","volume":"34","author":"Markones","year":"2018","journal-title":"Langmuir"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.bbamem.2019.03.012","article-title":"Effect of sterol structure on ordered membrane domain (raft) stability in symmetric and asymmetric vesicles","volume":"1861","author":"London","year":"2019","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1021\/acs.accounts.9b00300","article-title":"Membrane Structure\u2013Function Insights from Asymmetric Lipid Vesicles","volume":"52","author":"London","year":"2019","journal-title":"Acc. Chem. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S0006-291X(02)00905-1","article-title":"Solubility of amphiphiles in membranes: Influence of phase properties and amphiphile head group","volume":"296","author":"Estronca","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1021\/jp075149c","article-title":"Passive Transport of C60 Fullerenes through a Lipid Membrane:\u2009 A Molecular Dynamics Simulation Study","volume":"112","author":"Bedrov","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1039\/c0sm00136h","article-title":"Permeability of drugs and hormones through a lipid bilayer: Insights from dual-resolution molecular dynamics","volume":"6","author":"Orsi","year":"2010","journal-title":"Soft Matter"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1021\/acs.jcim.2c00767","article-title":"Modeling the Effect of Hydrophobicity on the Passive Permeation of Solutes across a Bacterial Model Membrane","volume":"62","author":"Sousa","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5954","DOI":"10.1021\/acs.chemrev.8b00486","article-title":"Molecular Dynamics Simulations of Membrane Permeability","volume":"119","author":"Venable","year":"2019","journal-title":"Chem. Rev."}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/13\/6\/551\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:41:36Z","timestamp":1760125296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/13\/6\/551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":100,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["membranes13060551"],"URL":"https:\/\/doi.org\/10.3390\/membranes13060551","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]}}}