A Method to Predict Blood-Brain Barrier Permeability of Drug-Like Compounds Using Molecular Dynamics Simulations

Biophysical Journal

Volumn 107, Issue 3, 2014, Pages 630-641

  Carpenter, Timothy S ^a   Kirshner, Daniel A ^a   Lau, Edmond Y ^a   Wong, Sergio E ^a   Nilmeier, Jerome P ^a   Lightstone, Felice C ^a  

^a LAWRENCE LIVERMORE NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG;

BIOLOGICAL MODEL; BLOOD; BLOOD BRAIN BARRIER; CAPILLARY PERMEABILITY; METABOLISM; MOLECULAR DYNAMICS;

BLOOD-BRAIN BARRIER; CAPILLARY PERMEABILITY; MODELS, BIOLOGICAL; MOLECULAR DYNAMICS SIMULATION; PHARMACEUTICAL PREPARATIONS;

EID: 84905650309     PISSN: 00063495     EISSN: 15420086     Source Type: Journal    
DOI: 10.1016/j.bpj.2014.06.024     Document Type: Article

References (102)

1. A.M. Seddon, and D. Casey O. Ces Drug interactions with lipid membranes Chem. Soc. Rev. 38 2009 2509 2519
2. D.J. Wolak, and R.G. Thorne Diffusion of macromolecules in the brain: implications for drug delivery Mol. Pharm. 10 2013 1492 1504
3. W.A. Banks Characteristics of compounds that cross the blood-brain barrier BMC Neurol. 9 Suppl 1 2009 S3
4. P. Ballabh, A. Braun, and M. Nedergaard The blood-brain barrier: an overview: structure, regulation, and clinical implications Neurobiol. Dis. 16 2004 1 13
5. F. Prado-Prado, M. Escobar-Cubiella, and X. Garcia-Mera Review of bioinformatics and QSAR studies of beta-secretase inhibitors Curr. Bioinf. 6 2011 3 15
6. P.D. Dobson, and D.B. Kell Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat. Rev. Drug Discov. 7 2008 205 220
7. M.N. Pangalos, L.E. Schechter, and O. Hurko Drug development for CNS disorders: strategies for balancing risk and reducing attrition Nat. Rev. Drug Discov. 6 2007 521 532
8. G.W. Ajay, G.W. Bemis, and M.A. Murcko Designing libraries with CNS activity J. Med. Chem. 42 1999 4942 4951
9. M. Adenot, and R. Lahana Blood-brain barrier permeation models: discriminating between potential CNS and non-CNS drugs including P-glycoprotein substrates J. Chem. Inf. Comput. Sci. 44 2004 239 248
10. Y.H. Zhao, and M.H. Abraham D.P. Reynolds Predicting penetration across the blood-brain barrier from simple descriptors and fragmentation schemes J. Chem. Inf. Model. 47 2007 170 175
11. I. Martin Prediction of blood-brain barrier penetration: are we missing the point? Drug Discov. Today 9 2004 161 162
12. W.M. Pardridge Log(BB), PS products and in silico models of drug brain penetration Drug Discov. Today 9 2004 392 393
13. Y. Takasato, S.I. Rapoport, and Q.R. Smith An in situ brain perfusion technique to study cerebrovascular transport in the rat Am. J. Physiol. 247 1984 H484 H493
14. E.M. Renkin Capillary permeability to lipid-soluble molecules Am. J. Physiol. 168 1952 538 545
15. C. Crone The permeability of capillaries in various organs as determined by use of the 'indicator diffusion' method Acta Physiol. Scand. 58 1963 292 305
16. M. Kansy, F. Senner, and K. Gubernator Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes J. Med. Chem. 41 1998 1007 1010
17. L. Di, and E.H. Kerns G.T. Carter High throughput artificial membrane permeability assay for blood-brain barrier Eur. J. Med. Chem. 38 2003 223 232
18. C. Masungi, and J. Mensch M.E. Brewster Parallel artificial membrane permeability assay (PAMPA) combined with a 10-day multiscreen Caco-2 cell culture as a tool for assessing new drug candidates Pharmazie 63 2008 194 199
19. J. Mensch, and A. Melis P. Augustijns Evaluation of various PAMPA models to identify the most discriminating method for the prediction of BBB permeability Eur. J. Pharm. Biopharm. 74 2010 495 502
20. O. Tsinman, and K. Tsinman A. Avdeef Physicochemical selectivity of the BBB microenvironment governing passive diffusion - matching with a porcine brain lipid extract artificial membrane permeability model Pharm. Res. 28 2011 337 363
21. S.D. Campbell, K.J. Regina, and E.D. Kharasch Significance of lipid composition in a blood-brain barrier-mimetic PAMPA assay J. Biomol. Screen. 19 2014 437 444
22. A. Könczöl, and J. Müller G.T. Balogh Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery J. Nat. Prod. 76 2013 655 663
23. C.Y. Yang, and S.J. Cai C. Pidgeon Immobilized artificial membranes - screens for drug membrane interactions Adv. Drug Deliv. Rev. 23 1997 229 256
24. S. Ong, H. Liu, and C. Pidgeon Immobilized-artificial-membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability J. Chromatogr. A 728 1996 113 128
25. A. Taillardat-Ertschinger, and A. Galland B. Testa Immobilized artificial membrane liquid chromatography: proposed guidelines for technical optimization of retention measurements J. Chromatogr. A 953 2002 39 53
26. D. Verzele, and F. Lynen P. Sandra Development of the first sphingomyelin biomimetic stationary phase for immobilized artificial membrane (IAM) chromatography Chem. Commun. (Camb.) 48 2012 1162 1164
27. T. Osterberg, M. Svensson, and P. Lundahl Chromatographic retention of drug molecules on immobilized liposomes prepared from egg phospholipids and from chemically pure phospholipids Eur. J. Pharm. Sci. 12 2001 427 439
28. P. Stenberg, and U. Norinder P. Artursson Experimental and computational screening models for the prediction of intestinal drug absorption J. Med. Chem. 44 2001 1927 1937
29. X. Liu, and M. Tu B.J. Smith Development of a computational approach to predict blood-brain barrier permeability Drug Metab. Dispos. 32 2004 132 139
30. U. Norinder, and M. Haeberlein Computational approaches to the prediction of the blood-brain distribution Adv. Drug Deliv. Rev. 54 2002 291 313
31. Y. Fan, and R. Unwalla C. Humblet Insights for predicting blood-brain barrier penetration of CNS targeted molecules using QSPR approaches J. Chem. Inf. Model. 50 2010 1123 1133
32. A.R. Katritzky, and M. Kuanar A. Varnek Correlation of blood-brain penetration using structural descriptors Bioorg. Med. Chem. 14 2006 4888 4917
33. Z.Y. Wu, and J. Pan A. Zhou Comparison of prediction models for blood brain barrier permeability and analysis of the molecular descriptors Pharmazie 67 2012 628 634
34. D.W. Borhani, and D.E. Shaw The future of molecular dynamics simulations in drug discovery J. Comput. Aided Mol. Des. 26 2012 15 26
35. Y. Deng, and B. Roux Computations of standard binding free energies with molecular dynamics simulations J. Phys. Chem. B 113 2009 2234 2246
36. P.F. Devaux Static and dynamic lipid asymmetry in cell membranes Biochemistry 30 1991 1163 1173
37. D. Bemporad, J.W. Essex, and C. Luttmann Permeation of small molecules through a lipid bilayer: a computer simulation study J. Phys. Chem. B 108 2004 4875 4884
38. M. Orsi, and J.W. Essex Permeability of drugs and hormones through a lipid bilayer: insights from dual-resolution molecular dynamics Soft Matter 6 2010 3797 3808
39. B.W. Holland, C.G. Gray, and B. Tomberli Calculating diffusion and permeability coefficients with the oscillating forward-reverse method Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 86 2012 036707
40. M.B. Boggara, and R. Krishnamoorti Partitioning of nonsteroidal antiinflammatory drugs in lipid membranes: a molecular dynamics simulation study Biophys. J. 98 2010 586 595
41. J.L. MacCallum, W.F.D. Bennett, and D.P. Tieleman Distribution of amino acids in a lipid bilayer from computer simulations Biophys. J. 94 2008 3393 3404
42. S.J. Marrink, and H.J.C. Berendsen Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations J. Phys. Chem. 100 1996 16729 16738
43. P. Crivori, and G. Cruciani B. Testa Predicting blood-brain barrier permeation from three-dimensional molecular structure J. Med. Chem. 43 2000 2204 2216
44. W.M. Pardridge Transport of protein-bound hormones into tissues in vivo Endocr. Rev. 2 1981 103 123
45. F. Ooms, and P. Weber B. Testa A simple model to predict blood-brain barrier permeation from 3D molecular fields Biochim. Biophys. Acta 1587 2002 118 125
46. H. Li, and C.W. Yap Y.Z. Chen Effect of selection of molecular descriptors on the prediction of blood-brain barrier penetrating and nonpenetrating agents by statistical learning methods J. Chem. Inf. Model. 45 2005 1376 1384
47. B. Hess, and C. Kutzner E. Lindahl GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation J. Chem. Theory Comput. 4 2008 435 447
48. O. Berger, O. Edholm, and F. Jähnig Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature Biophys. J. 72 1997 2002 2013
49. C. Oostenbrink, and A. Villa W.F. van Gunsteren A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6 J. Comput. Chem. 25 2004 1656 1676
50. H.J.C. Berendsen, and J.P.M. Postma J. Hermans Interaction models for water in relation to protein hydration B. Pullman, Intermolecular Forces 1981 D. Reidel Dordrecht, The Netherlands 331 342
51. W.G. Hoover Canonical dynamics: equilibrium phase-space distributions Phys. Rev. A 31 1985 1695 1697
52. M. Parrinello, and A. Rahman Polymorphic transitions in single-crystals - a new molecular-dynamics method J. Appl. Phys. 52 1981 7182 7190
53. B. Hess, and H. Bekker J.G.E.M. Fraaije LINCS: a linear constraint solver for molecular simulations J. Comput. Chem. 18 1997 1463 1472
54. T. Darden, D. York, and L. Pedersen Particle mesh Ewald - an N.log(N) method for Ewald sums in large systems J. Chem. Phys. 98 1993 10089 10092
55. U. Essmann, L. Perera, and M. Berkowitz A smooth particle mesh Ewald Method J. Chem. Phys. 103 1995 8577 8593
56. A.K. Malde, and L. Zuo A.E. Mark An automated force field topology builder (ATB) and repository: version 1.0 J. Chem. Theory Comput. 7 2011 4026 4037
57. A.D. Becke Density-functional thermochemistry. 3. The role of exact exchange J. Chem. Phys. 98 1993 5648 5652
58. C. Lee, W. Yang, and R.G. Parr Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B Condens. Matter 37 1988 785 789
59. J.P. Perdew, and Y. Wang Accurate and simple analytic representation of the electron-gas correlation energy Phys. Rev. B Condens. Matter 45 1992 13244 13249
60. U.C. Singh, and P.A. Kollman An approach to computing electrostatic charges for molecules J. Comput. Chem. 5 1984 129 145
61. S. Kumar, and J.M. Rosenberg P.A. Kollman The weighted histogram analysis method for free-energy calculations on biomolecules. 1. The method J. Comput. Chem. 13 1992 1011 1021
62. G. Hummer Position-dependent diffusion coefficients and free energies from Bayesian analysis of equilibrium and replica molecular dynamics simulations New J. Phys. 7 2005 34
63. S.J. Marrink, and H.J.C. Berendsen Simulation of water transport through a lipid membrane J. Phys. Chem. 98 1994 4155 4168
64. T.B. Rosenthal The effect of temperature on the pH of blood and plasma in vitro J. Biol. Chem. 173 1948 25 30
65. A. Roos, and W.F. Boron Intracellular pH Physiol. Rev. 61 1981 296 434
66. M. Paloncýová, K. Berka, and M. Otyepka Molecular insight into affinities of drugs and their metabolites to lipid bilayers J. Phys. Chem. B 117 2013 2403 2410
67. J.L. MacCallum, W.F. Bennett, and D.P. Tieleman Partitioning of amino acid side chains into lipid bilayers: results from computer simulations and comparison to experiment J. Gen. Physiol. 129 2007 371 377
68. M. Paloncýová, K. Berka, and M. Otyepka Convergence of free energy profile of coumarin in lipid bilayer J. Chem. Theory Comput. 8 2012 1200 1211
69. J. Haorah, and D. Heilman Y. Persidsky Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise Alcohol. Clin. Exp. Res. 29 2005 999 1009
70. Raub, T. J., 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.
71. H. Murakami, and H. Takanaga Y. Sawada Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique Am. J. Physiol. Heart Circ. Physiol. 279 2000 H1022 H1028
72. R. Zhao, J.C. Kalvass, and G.M. Pollack Assessment of blood-brain barrier permeability using the in situ mouse brain perfusion technique Pharm. Res. 26 2009 1657 1664
73. L. Zhang, and H. Zhu A. Tropsha QSAR modeling of the blood-brain barrier permeability for diverse organic compounds Pharm. Res. 25 2008 1902 1914
74. A. Shayanfar, S. Soltani, and A. Jouyban Prediction of blood-brain distribution: effect of ionization Biol. Pharm. Bull. 34 2011 266 271
75. P. Garg, and J. Verma In silico prediction of blood brain barrier permeability: an Artificial Neural Network model J. Chem. Inf. Model. 46 2006 289 297
76. J.M.R. Parepally, H. Mandula, and Q.R. Smith Brain uptake of nonsteroidal anti-inflammatory drugs: ibuprofen, flurbiprofen, and indomethacin Pharm. Res. 23 2006 873 881
77. M. Karelson, and D. Dobchev G. Karelson Correlation of blood-brain penetration and human serum albumin binding with theoretical descriptors ARKIVOC 16 2008 38 60
78. D.R. Jones, and S.D. Hall G.R. Wilkinson Brain uptake of benzodiazepines: effects of lipophilicity and plasma protein binding J. Pharmacol. Exp. Ther. 245 1988 816 822
79. J. Shen, and Y. Du Y. Tang In silico prediction of blood-brain partitioning using a chemometric method called genetic algorithm based variable selection QSAR Comb. Sci. 27 2008 704 717
80. S. Cisternino, and H. Chapy J.M. Scherrmann Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier AAPS J. 15 2013 299 307
81. S.G. Summerfield, and K. Read P. Jeffrey Central nervous system drug disposition: the relationship between in situ brain permeability and brain free fraction J. Pharmacol. Exp. Ther. 322 2007 205 213
82. T. Salminen, A. Pulli, and J. Taskinen Relationship between immobilized artificial membrane chromatographic retention and the brain penetration of structurally diverse drugs J. Pharm. Biomed. Anal. 15 1997 469 477
83. J.H. de Smidt, and J.G. Fokkens D.J. Crommelin Dissolution of theophylline monohydrate and anhydrous theophylline in buffer solutions J. Pharm. Sci. 75 1986 497 501
84. M. Grassi, I. Colombo, and R. Lapasin Experimental determination of the theophylline diffusion coefficient in swollen sodium-alginate membranes J. Control. Release 76 2001 93 105
85. P. Mark, and L. Nilsson Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K J. Phys. Chem. A 105 2001 9954 9960
86. M. Orsi, W.E. Sanderson, and J.W. Essex Permeability of small molecules through a lipid bilayer: a multiscale simulation study J. Phys. Chem. B 113 2009 12019 12029
87. J.M. Luco Prediction of the brain-blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling J. Chem. Inf. Comput. Sci. 39 1999 396 404
88. E. Deconinck, and M.H. Zhang Y. Vander Heyden Classification tree models for the prediction of blood-brain barrier passage of drugs J. Chem. Inf. Model. 46 2006 1410 1419
89. K. Rose, L.H. Hall, and L.B. Kier Modeling blood-brain barrier partitioning using the electrotopological state J. Chem. Inf. Comput. Sci. 42 2002 651 666
90. M.A. Cabrera, and M. Bermejo R. Ramos TOPS-MODE approach for the prediction of blood-brain barrier permeation J. Pharm. Sci. 93 2004 1701 1717
91. C. Suenderhauf, F. Hammann, and J. Huwyler Computational prediction of blood-brain barrier permeability using decision tree induction Molecules 17 2012 10429 10445
92. R.C. Young, and R.C. Mitchell T.J. Wilks Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists J. Med. Chem. 31 1988 656 671
93. V.A. Levin Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability J. Med. Chem. 23 1980 682 684
94. J.A. Gratton, and M.H. Abraham H.S. Chadha Molecular factors influencing drug transfer across the blood-brain barrier J. Pharm. Pharmacol. 49 1997 1211 1216
95. M.H. Abraham The factors that influence permeation across the blood-brain barrier Eur. J. Med. Chem. 39 2004 235 240
96. S. Weaver, and M.P. Gleeson The importance of the domain of applicability in QSAR modeling J. Mol. Graph. Model. 26 2008 1315 1326
97. X.C. Fu, and G.P. Wang J.Q. Gao Predicting blood-brain barrier penetration from molecular weight and number of polar atoms Eur. J. Pharm. Biopharm. 70 2008 462 466
98. M. De Vrieze, and F. Lynen P. Sandra Predicting drug penetration across the blood-brain barrier: comparison of micellar liquid chromatography and immobilized artificial membrane liquid chromatography Anal. Bioanal. Chem. 405 2013 6029 6041
99. C. Neale, and C. Madill R. Pomès Accelerating convergence in molecular dynamics simulations of solutes in lipid membranes by conducting a random walk along the bilayer normal J. Chem. Theory Comput. 9 2013 3686 3703
100. C.L. Wennberg, D. van der Spoel, and J.S. Hub Large influence of cholesterol on solute partitioning into lipid membranes J. Am. Chem. Soc. 134 2012 5351 5361
101. F. Meng, and W. Xu Drug permeability prediction using PMF method J. Mol. Model. 19 2013 991 997
102. N.M. Garrido, and A.J. Queimada I.G. Economou 1-Octanol/water partition coefficients of n-alkanes from molecular simulations of absolute solvation free energies J. Chem. Theory Comput. 5 2009 2436 2446