{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:27:17Z","timestamp":1791516437869,"version":"4.3.4"},"reference-count":102,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T00:00:00Z","timestamp":1438732800000},"content-version":"vor","delay-in-days":369,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007000","name":"Laboratory Directed Research and Development","doi-asserted-by":"publisher","award":["12-SI-004"],"award-info":[{"award-number":["12-SI-004"]}],"id":[{"id":"10.13039\/100007000","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006227","name":"U.S. Department of Energy by Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["DE-AC52-07NA27344"],"award-info":[{"award-number":["DE-AC52-07NA27344"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006227","name":"U.S. Department of Energy by Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["LLNL-JRNL-648046"],"award-info":[{"award-number":["LLNL-JRNL-648046"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["biophysj.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2014,8]]},"DOI":"10.1016\/j.bpj.2014.06.024","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T15:47:05Z","timestamp":1407253625000},"page":"630-641","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":293,"title":["A Method to Predict Blood-Brain Barrier Permeability of Drug-Like Compounds Using Molecular Dynamics Simulations"],"prefix":"10.1016","volume":"107","author":[{"given":"Timothy\u00a0S.","family":"Carpenter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0A.","family":"Kirshner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond\u00a0Y.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio\u00a0E.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome\u00a0P.","family":"Nilmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice\u00a0C.","family":"Lightstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpj.2014.06.024_bib1","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1039\/b813853m","article-title":"Drug interactions with lipid membranes","volume":"38","author":"Seddon","year":"2009","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.bpj.2014.06.024_bib2","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1021\/mp300495e","article-title":"Diffusion of macromolecules in the brain: implications for drug delivery","volume":"10","author":"Wolak","year":"2013","journal-title":"Mol. Pharm."},{"issue":"Suppl 1","key":"10.1016\/j.bpj.2014.06.024_bib3","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1471-2377-9-S1-S3","article-title":"Characteristics of compounds that cross the blood-brain barrier","volume":"9","author":"Banks","year":"2009","journal-title":"BMC Neurol."},{"key":"10.1016\/j.bpj.2014.06.024_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The blood-brain barrier: an overview: structure, regulation, and clinical implications","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.bpj.2014.06.024_bib5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/157489311795222428","article-title":"Review of bioinformatics and QSAR studies of beta-secretase inhibitors","volume":"6","author":"Prado-Prado","year":"2011","journal-title":"Curr. Bioinf."},{"key":"10.1016\/j.bpj.2014.06.024_bib6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd2438","article-title":"Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule?","volume":"7","author":"Dobson","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bpj.2014.06.024_bib7","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nrd2094","article-title":"Drug development for CNS disorders: strategies for balancing risk and reducing attrition","volume":"6","author":"Pangalos","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bpj.2014.06.024_bib8","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1021\/jm990017w","article-title":"Designing libraries with CNS activity","volume":"42","author":"Ajay","year":"1999","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/ci034205d","article-title":"Blood-brain barrier permeation models: discriminating between potential CNS and non-CNS drugs including P-glycoprotein substrates","volume":"44","author":"Adenot","year":"2004","journal-title":"J.\u00a0Chem. Inf. Comput. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1021\/ci600312d","article-title":"Predicting penetration across the blood-brain barrier from simple descriptors and fragmentation schemes","volume":"47","author":"Zhao","year":"2007","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1359-6446(03)02961-1","article-title":"Prediction of blood-brain barrier penetration: are we missing the point?","volume":"9","author":"Martin","year":"2004","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.bpj.2014.06.024_bib12","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S1359-6446(04)03065-X","article-title":"Log(BB), PS products and in\u00a0silico models of drug brain penetration","volume":"9","author":"Pardridge","year":"2004","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.bpj.2014.06.024_bib13","first-page":"H484","article-title":"An in\u00a0situ brain perfusion technique to study cerebrovascular transport in the rat","volume":"247","author":"Takasato","year":"1984","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.bpj.2014.06.024_bib14","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1152\/ajplegacy.1952.168.2.538","article-title":"Capillary permeability to lipid-soluble molecules","volume":"168","author":"Renkin","year":"1952","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.bpj.2014.06.024_bib15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1748-1716.1963.tb02652.x","article-title":"The permeability of capillaries in various organs as determined by use of the \u2018indicator diffusion\u2019 method","volume":"58","author":"Crone","year":"1963","journal-title":"Acta Physiol. Scand."},{"key":"10.1016\/j.bpj.2014.06.024_bib16","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/jm970530e","article-title":"Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes","volume":"41","author":"Kansy","year":"1998","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0223-5234(03)00012-6","article-title":"High throughput artificial membrane permeability assay for blood-brain barrier","volume":"38","author":"Di","year":"2003","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib18","first-page":"194","article-title":"Parallel artificial membrane permeability assay (PAMPA) combined with a 10-day multiscreen Caco-2 cell culture as a tool for assessing new drug candidates","volume":"63","author":"Masungi","year":"2008","journal-title":"Pharmazie"},{"key":"10.1016\/j.bpj.2014.06.024_bib19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ejpb.2010.01.003","article-title":"Evaluation of various PAMPA models to identify the most discriminating method for the prediction of BBB permeability","volume":"74","author":"Mensch","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.bpj.2014.06.024_bib20","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11095-010-0280-x","article-title":"Physicochemical selectivity of the BBB microenvironment governing passive diffusion\u2014matching with a porcine brain lipid extract artificial membrane permeability model","volume":"28","author":"Tsinman","year":"2011","journal-title":"Pharm. Res."},{"key":"10.1016\/j.bpj.2014.06.024_bib21","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1177\/1087057113497981","article-title":"Significance of lipid composition in a blood-brain barrier-mimetic PAMPA assay","volume":"19","author":"Campbell","year":"2014","journal-title":"J.\u00a0Biomol. Screen."},{"key":"10.1016\/j.bpj.2014.06.024_bib22","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1021\/np300882f","article-title":"Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery","volume":"76","author":"K\u00f6ncz\u00f6l","year":"2013","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.bpj.2014.06.024_bib23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0169-409X(96)00438-3","article-title":"Immobilized artificial membranes - screens for drug membrane interactions","volume":"23","author":"Yang","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bpj.2014.06.024_bib24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0021-9673(95)00837-3","article-title":"Immobilized-artificial-membrane\u00a0chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability","volume":"728","author":"Ong","year":"1996","journal-title":"J. Chromatogr. A"},{"key":"10.1016\/j.bpj.2014.06.024_bib25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0021-9673(02)00119-X","article-title":"Immobilized artificial membrane liquid chromatography: proposed guidelines for technical optimization of retention measurements","volume":"953","author":"Taillardat-Ertschinger","year":"2002","journal-title":"J.\u00a0Chromatogr. A"},{"key":"10.1016\/j.bpj.2014.06.024_bib26","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1039\/C2CC16872C","article-title":"Development of the first sphingomyelin biomimetic stationary phase for immobilized artificial membrane (IAM) chromatography","volume":"48","author":"Verzele","year":"2012","journal-title":"Chem. Commun. (Camb.)"},{"key":"10.1016\/j.bpj.2014.06.024_bib27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0928-0987(00)00183-4","article-title":"Chromatographic retention of drug molecules on immobilized liposomes prepared from egg phospholipids and from chemically pure phospholipids","volume":"12","author":"Osterberg","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib28","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1021\/jm001101a","article-title":"Experimental and computational screening models for the prediction of intestinal drug absorption","volume":"44","author":"Stenberg","year":"2001","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib29","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1124\/dmd.32.1.132","article-title":"Development of a computational approach to predict blood-brain barrier permeability","volume":"32","author":"Liu","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.bpj.2014.06.024_bib30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0169-409X(02)00005-4","article-title":"Computational approaches to the prediction of the blood-brain distribution","volume":"54","author":"Norinder","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bpj.2014.06.024_bib31","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1021\/ci900384c","article-title":"Insights for predicting blood-brain barrier penetration of CNS targeted molecules using QSPR approaches","volume":"50","author":"Fan","year":"2010","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib32","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1016\/j.bmc.2006.03.012","article-title":"Correlation of blood-brain penetration using structural descriptors","volume":"14","author":"Katritzky","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib33","first-page":"628","article-title":"Comparison of prediction models for blood brain barrier permeability and analysis of the molecular descriptors","volume":"67","author":"Wu","year":"2012","journal-title":"Pharmazie"},{"key":"10.1016\/j.bpj.2014.06.024_bib34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10822-011-9517-y","article-title":"The future of molecular dynamics simulations in drug discovery","volume":"26","author":"Borhani","year":"2012","journal-title":"J.\u00a0Comput. Aided Mol. Des."},{"key":"10.1016\/j.bpj.2014.06.024_bib35","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1021\/jp807701h","article-title":"Computations of standard binding free energies with molecular dynamics simulations","volume":"113","author":"Deng","year":"2009","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2014.06.024_bib36","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1021\/bi00219a001","article-title":"Static and dynamic lipid asymmetry in cell membranes","volume":"30","author":"Devaux","year":"1991","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2014.06.024_bib37","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.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2014.06.024_bib38","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":"10.1016\/j.bpj.2014.06.024_bib39","doi-asserted-by":"crossref","first-page":"036707","DOI":"10.1103\/PhysRevE.86.036707","article-title":"Calculating diffusion and permeability coefficients with the oscillating forward-reverse method","volume":"86","author":"Holland","year":"2012","journal-title":"Phys. Rev. E Stat. Nonlin. Soft Matter Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib40","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.bpj.2009.10.046","article-title":"Partitioning of nonsteroidal antiinflammatory drugs in lipid membranes: a molecular dynamics simulation study","volume":"98","author":"Boggara","year":"2010","journal-title":"Biophys.\u00a0J."},{"key":"10.1016\/j.bpj.2014.06.024_bib41","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1529\/biophysj.107.112805","article-title":"Distribution of amino acids in a lipid bilayer from computer simulations","volume":"94","author":"MacCallum","year":"2008","journal-title":"Biophys.\u00a0J."},{"key":"10.1016\/j.bpj.2014.06.024_bib42","doi-asserted-by":"crossref","first-page":"16729","DOI":"10.1021\/jp952956f","article-title":"Permeation process of\u00a0small molecules across lipid membranes studied by molecular dynamics simulations","volume":"100","author":"Marrink","year":"1996","journal-title":"J.\u00a0Phys. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib43","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1021\/jm990968+","article-title":"Predicting blood-brain barrier permeation from three-dimensional molecular structure","volume":"43","author":"Crivori","year":"2000","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1210\/edrv-2-1-103","article-title":"Transport of protein-bound hormones into tissues in\u00a0vivo","volume":"2","author":"Pardridge","year":"1981","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.bpj.2014.06.024_bib45","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0925-4439(02)00074-1","article-title":"A simple model to predict blood-brain barrier permeation from 3D molecular fields","volume":"1587","author":"Ooms","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.bpj.2014.06.024_bib46","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1021\/ci050135u","article-title":"Effect of selection of molecular descriptors on the prediction of blood-brain barrier penetrating and nonpenetrating agents by statistical learning methods","volume":"45","author":"Li","year":"2005","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib47","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.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2014.06.024_bib48","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.\u00a0J."},{"key":"10.1016\/j.bpj.2014.06.024_bib49","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/jcc.20090","article-title":"A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6","volume":"25","author":"Oostenbrink","year":"2004","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib50","series-title":"Intermolecular Forces","first-page":"331","article-title":"Interaction models for water in relation to protein hydration","author":"Berendsen","year":"1981"},{"key":"10.1016\/j.bpj.2014.06.024_bib51","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical dynamics: equilibrium phase-space distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys. Rev. A"},{"key":"10.1016\/j.bpj.2014.06.024_bib52","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single-crystals - a new molecular-dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J.\u00a0Appl. Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib53","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.\u00a0Comput. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib54","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald - an N.log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J.\u00a0Chem. Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib55","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.\u00a0Chem. Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib56","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1021\/ct200196m","article-title":"An automated force field topology builder (ATB) and repository: version 1.0","volume":"7","author":"Malde","year":"2011","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2014.06.024_bib57","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","article-title":"Density-functional thermochemistry. 3. The role of exact exchange","volume":"98","author":"Becke","year":"1993","journal-title":"J.\u00a0Chem. Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib58","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B Condens. Matter"},{"key":"10.1016\/j.bpj.2014.06.024_bib59","doi-asserted-by":"crossref","first-page":"13244","DOI":"10.1103\/PhysRevB.45.13244","article-title":"Accurate and simple analytic representation of the electron-gas correlation energy","volume":"45","author":"Perdew","year":"1992","journal-title":"Phys. Rev. B Condens. Matter"},{"key":"10.1016\/j.bpj.2014.06.024_bib60","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jcc.540050204","article-title":"An approach to computing electrostatic charges for molecules","volume":"5","author":"Singh","year":"1984","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib61","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/jcc.540130812","article-title":"The weighted histogram analysis method for free-energy calculations on biomolecules. 1. The method","volume":"13","author":"Kumar","year":"1992","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1088\/1367-2630\/7\/1\/034","article-title":"Position-dependent diffusion coefficients and free energies from Bayesian analysis of equilibrium and replica molecular dynamics simulations","volume":"7","author":"Hummer","year":"2005","journal-title":"New J. Phys."},{"key":"10.1016\/j.bpj.2014.06.024_bib63","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.\u00a0Phys. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib64","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0021-9258(18)35552-2","article-title":"The effect of temperature on the pH of blood and plasma in\u00a0vitro","volume":"173","author":"Rosenthal","year":"1948","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib65","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1152\/physrev.1981.61.2.296","article-title":"Intracellular pH","volume":"61","author":"Roos","year":"1981","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.bpj.2014.06.024_bib66","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1021\/jp311802x","article-title":"Molecular insight into affinities of drugs and their metabolites to lipid bilayers","volume":"117","author":"Palonc\u00fdov\u00e1","year":"2013","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2014.06.024_bib67","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1085\/jgp.200709745","article-title":"Partitioning of amino acid side chains into lipid bilayers: results from computer simulations and comparison to experiment","volume":"129","author":"MacCallum","year":"2007","journal-title":"J.\u00a0Gen. Physiol."},{"key":"10.1016\/j.bpj.2014.06.024_bib68","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":"Palonc\u00fdov\u00e1","year":"2012","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2014.06.024_bib69","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1097\/01.ALC.0000166944.79914.0A","article-title":"Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise","volume":"29","author":"Haorah","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.bpj.2014.06.024_bib70","unstructured":"Raub, T. J., \u2026. 2006. Early preclinical evaluation of brain exposure in support of hit identification and lead optimization. in Optimizing the Drug-Like Properties of Leads in Drug Discovery. http:\/\/link.springer.com\/chapter\/10.1007\/978-0-387-44961-6_16."},{"key":"10.1016\/j.bpj.2014.06.024_bib71","doi-asserted-by":"crossref","first-page":"H1022","DOI":"10.1152\/ajpheart.2000.279.3.H1022","article-title":"Comparison of blood-brain barrier permeability in mice and rats using in\u00a0situ brain perfusion technique","volume":"279","author":"Murakami","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.bpj.2014.06.024_bib72","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1007\/s11095-009-9876-4","article-title":"Assessment of blood-brain barrier permeability using the in\u00a0situ mouse brain perfusion technique","volume":"26","author":"Zhao","year":"2009","journal-title":"Pharm. Res."},{"key":"10.1016\/j.bpj.2014.06.024_bib73","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1007\/s11095-008-9609-0","article-title":"QSAR modeling of the blood-brain barrier permeability for diverse organic compounds","volume":"25","author":"Zhang","year":"2008","journal-title":"Pharm. Res."},{"key":"10.1016\/j.bpj.2014.06.024_bib74","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1248\/bpb.34.266","article-title":"Prediction of blood-brain distribution: effect of ionization","volume":"34","author":"Shayanfar","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.bpj.2014.06.024_bib75","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/ci050303i","article-title":"In silico prediction of blood brain barrier permeability: an Artificial Neural Network model","volume":"46","author":"Garg","year":"2006","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib76","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s11095-006-9905-5","article-title":"Brain uptake of nonsteroidal anti-inflammatory drugs: ibuprofen, flurbiprofen, and indomethacin","volume":"23","author":"Parepally","year":"2006","journal-title":"Pharm. Res."},{"key":"10.1016\/j.bpj.2014.06.024_bib77","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3998\/ark.5550190.0009.g05","article-title":"Correlation of blood-brain penetration and human serum albumin binding with theoretical descriptors","volume":"16","author":"Karelson","year":"2008","journal-title":"ARKIVOC"},{"key":"10.1016\/j.bpj.2014.06.024_bib78","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S0022-3565(25)24108-8","article-title":"Brain uptake of benzodiazepines: effects of lipophilicity and plasma protein binding","volume":"245","author":"Jones","year":"1988","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.bpj.2014.06.024_bib79","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/qsar.200710129","article-title":"In silico prediction of blood-brain partitioning using a chemometric method called genetic algorithm based variable selection","volume":"27","author":"Shen","year":"2008","journal-title":"QSAR Comb. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib80","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1208\/s12248-012-9434-6","article-title":"Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier","volume":"15","author":"Cisternino","year":"2013","journal-title":"AAPS\u00a0J."},{"key":"10.1016\/j.bpj.2014.06.024_bib81","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1124\/jpet.107.121525","article-title":"Central nervous system drug disposition: the relationship between in\u00a0situ brain permeability and brain free fraction","volume":"322","author":"Summerfield","year":"2007","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.bpj.2014.06.024_bib82","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0731-7085(96)01883-3","article-title":"Relationship between immobilized artificial membrane chromatographic retention and the brain penetration of structurally diverse drugs","volume":"15","author":"Salminen","year":"1997","journal-title":"J.\u00a0Pharm. Biomed. Anal."},{"key":"10.1016\/j.bpj.2014.06.024_bib83","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/jps.2600750515","article-title":"Dissolution of theophylline monohydrate and anhydrous theophylline in buffer solutions","volume":"75","author":"de Smidt","year":"1986","journal-title":"J.\u00a0Pharm. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib84","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0168-3659(01)00424-2","article-title":"Experimental determination of the theophylline diffusion coefficient in swollen sodium-alginate membranes","volume":"76","author":"Grassi","year":"2001","journal-title":"J.\u00a0Control. Release"},{"key":"10.1016\/j.bpj.2014.06.024_bib85","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J.\u00a0Phys. Chem. A"},{"key":"10.1016\/j.bpj.2014.06.024_bib86","doi-asserted-by":"crossref","first-page":"12019","DOI":"10.1021\/jp903248s","article-title":"Permeability of small molecules through a lipid bilayer: a multiscale simulation study","volume":"113","author":"Orsi","year":"2009","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2014.06.024_bib87","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/ci980411n","article-title":"Prediction of the brain-blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling","volume":"39","author":"Luco","year":"1999","journal-title":"J.\u00a0Chem. Inf. Comput. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib88","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1021\/ci050518s","article-title":"Classification tree models for the prediction of blood-brain barrier passage of drugs","volume":"46","author":"Deconinck","year":"2006","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib89","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1021\/ci010127n","article-title":"Modeling blood-brain barrier partitioning using the electrotopological state","volume":"42","author":"Rose","year":"2002","journal-title":"J.\u00a0Chem. Inf. Comput. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib90","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jps.20081","article-title":"TOPS-MODE approach for the prediction of blood-brain barrier permeation","volume":"93","author":"Cabrera","year":"2004","journal-title":"J.\u00a0Pharm. Sci."},{"key":"10.1016\/j.bpj.2014.06.024_bib91","doi-asserted-by":"crossref","first-page":"10429","DOI":"10.3390\/molecules170910429","article-title":"Computational prediction of blood-brain barrier permeability using decision tree induction","volume":"17","author":"Suenderhauf","year":"2012","journal-title":"Molecules"},{"key":"10.1016\/j.bpj.2014.06.024_bib92","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1021\/jm00398a028","article-title":"Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists","volume":"31","author":"Young","year":"1988","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib93","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1021\/jm00180a022","article-title":"Relationship of octanol\/water partition coefficient and molecular weight to rat brain capillary permeability","volume":"23","author":"Levin","year":"1980","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib94","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/j.2042-7158.1997.tb06072.x","article-title":"Molecular factors influencing drug transfer across the blood-brain barrier","volume":"49","author":"Gratton","year":"1997","journal-title":"J.\u00a0Pharm. Pharmacol."},{"key":"10.1016\/j.bpj.2014.06.024_bib95","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejmech.2003.12.004","article-title":"The factors that influence permeation across the blood-brain barrier","volume":"39","author":"Abraham","year":"2004","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib96","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.jmgm.2008.01.002","article-title":"The importance of the domain of applicability in QSAR modeling","volume":"26","author":"Weaver","year":"2008","journal-title":"J.\u00a0Mol. Graph. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib97","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.ejpb.2008.05.005","article-title":"Predicting blood-brain barrier penetration from molecular weight and number of polar atoms","volume":"70","author":"Fu","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.bpj.2014.06.024_bib98","doi-asserted-by":"crossref","first-page":"6029","DOI":"10.1007\/s00216-013-7015-x","article-title":"Predicting drug penetration across the blood-brain barrier: comparison of micellar liquid chromatography and immobilized artificial membrane liquid chromatography","volume":"405","author":"De Vrieze","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.bpj.2014.06.024_bib99","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.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2014.06.024_bib100","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1021\/ja211929h","article-title":"Large influence of cholesterol on solute partitioning into lipid membranes","volume":"134","author":"Wennberg","year":"2012","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2014.06.024_bib101","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00894-012-1655-1","article-title":"Drug permeability prediction using PMF method","volume":"19","author":"Meng","year":"2013","journal-title":"J.\u00a0Mol. Model."},{"key":"10.1016\/j.bpj.2014.06.024_bib102","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1021\/ct900214y","article-title":"1-Octanol\/water partition coefficients of n-alkanes from molecular simulations of absolute solvation free energies","volume":"5","author":"Garrido","year":"2009","journal-title":"J.\u00a0Chem. Theory Comput."}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000634951400664X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000634951400664X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T02:17:22Z","timestamp":1746325042000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000634951400664X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":102,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["S000634951400664X"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2014.06.024","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2014,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Method to Predict Blood-Brain Barrier Permeability of Drug-Like Compounds Using Molecular Dynamics Simulations","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2014.06.024","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}