Computational insights into function and inhibition of fatty acid amide hydrolase

European Journal of Medicinal Chemistry

Volumn 91, Issue , 2015, Pages 15-26

  Palermo, Giulia ^a,b   Rothlisberger, Ursula ^b   Cavalli, Andrea ^a,c   De Vivo, Marco ^a  

^a ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^b EPFL   (Switzerland)

^c UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; AMIDASE; AMIDE; ANANDAMIDE; ARACHIDONIC ACID DERIVATIVE; ENDOCANNABINOID; ENZYME INHIBITOR; FATTY-ACID AMIDE HYDROLASE; RECOMBINANT PROTEIN;

CATALYSIS; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME SUBSTRATE; MOLECULAR DYNAMICS; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN STRUCTURE; QUANTUM MECHANICS; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; GENE EXPRESSION; HUMAN; KINETICS; METABOLISM; MOLECULAR DOCKING; QUANTUM THEORY; RAT; SITE DIRECTED MUTAGENESIS; SYNTHESIS;

AMIDOHYDROLASES; ANIMALS; ARACHIDONIC ACIDS; ENDOCANNABINOIDS; ENZYME INHIBITORS; GENE EXPRESSION; HUMANS; KINETICS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; MUTAGENESIS, SITE-DIRECTED; POLYUNSATURATED ALKAMIDES; QUANTUM THEORY; RATS; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84921443528     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.09.037     Document Type: Review

References (124)

1. M.H. Bracey M.A. Hanson K.R. Masuda R.C. Stevens B.F. Cravatt Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling Science 298 2002 1793 1796
2. B.F. Cravatt D.K. Giang S.P. Mayfield D.L. Boger R.A. Lerner N.B. Gilula Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides Nature 384 1996 83 87
3. D. Piomelli The molecular logic of endocannabinoid signalling Nat. Rev. Neurosci. 4 2003 873 884
4. B.F. Cravatt O. Prospero-Garcia G. Siuzdak N.B. Gilula S.J. Henriksen D.L. Boger R.A. Lerner Chemical characterization of a family of brain lipids that induce sleep Science 268 1995 1506 1509
5. F. Desarnaud H. Cadas D. Piomelli Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization J. Biol. Chem. 270 1995 6030 6035
6. W.A. Devane L. Hanus A. Breuer R.G. Pertwee L.A. Stevenson G. Griffin D. Gibson A. Mandelbaum A. Etinger R. Mechoulam Isolation and structure of a brain constituent that binds to the cannabinoid receptor Science 258 1992 1946 1949
7. D.L. Boger R.A. Fecik J.E. Patterson H. Miyauchi M.P. Patricelli B.F. Cravatt Fatty acid amide hydrolase substrate specificity Bioorg. Med. Chem. Lett. 10 2000 2613 2616
8. G. Labar C. Bauvois F. Borel J.L. Ferrer J. Wouters D.M. Lambert Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling Chembiochem 11 2010 218 227
9. T. Sugiura S. Kondo A. Sukagawa S. Nakane A. Shinoda K. Itoh A. Yamashita K. Waku 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain Biochem. Biophys. Res. Comm. 215 1995 89 97
10. P. Campolongo B. Roozendaal V. Trezza V. Cuomo G. Astarita J. Fu J.L. McGaugh D. Piomelli Fat-induced satiety factor oleoylethanolamide enhances memory consolidation Proc. Natl. Acad. Sci. USA 106 2009 8027 8031
11. F. Rodriguez de Fonseca M. Navarro R. Gomez L. Escuredo F. Nava J. Fu E. Murillo-Rodriguez A. Giuffrida J. LoVerme S. Gaetani S. Kathuria C. Gall D. Piomelli An anorexic lipid mediator regulated by feeding Nature 414 2001 209 212
12. C. Solorzano C. Zhu N. Battista G. Astarita A. Lodola S. Rivara M. Mor R. Russo M. Maccarrone F. Antonietti A. Duranti A. Tontini S. Cuzzocrea G. Tarzia D. Piomelli Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation Proc. Natl. Acad. Sci. USA 106 2009 20966 20971
13. A. Makriyannis 2012 division of medicinal chemistry award address. Trekking the cannabinoid road: a personal perspective J. Med. Chem. 57 2014 3891 3911
14. B.F. Cravatt K. Demarest M.P. Patricelli M.H. Bracey D.K. Giang B.R. Martin A.H. Lichtman Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase Proc. Natl. Acad. Sci. USA 98 2001 9371 9376
15. M. Karsak E. Gaffal R. Date L. Wang-Eckhardt J. Rehnelt S. Petrosino K. Starowicz R. Steuder E. Schlicker B. Cravatt R. Mechoulam R. Buettner S. Werner V. Di Marzo T. Tuting A. Zimmer Attenuation of allergic contact dermatitis through the endocannabinoid system Science 316 2007 1494 1497
16. A.H. Lichtman C.C. Shelton T. Advani B.F. Cravatt Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia Pain 109 2004 319 327
17. K. Otrubova M. Brown M.S. McCormick G.W. Han S.T. O'Neal B.F. Cravatt R.C. Stevens A.H. Lichtman D.L. Boger Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues J. Am. Chem. Soc. 135 2013 6289 6299
18. L. Bertolacci E. Romeo M. Veronesi P. Magotti C. Albani M. Dionisi C. Lambruschini R. Scarpelli A. Cavalli M. De Vivo D. Piomelli G. Garau A binding site for nonsteroidal anti-inflammatory drugs in fatty acid amide hydrolase J. Am. Chem. Soc. 135 2013 22 25
19. A.D. Favia D. Habrant R. Scarpelli M. Migliore C. Albani S.M. Bertozzi M. Dionisi G. Tarozzo D. Piomelli A. Cavalli M. De Vivo Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor J. Med. Chem. 55 2012 8807 8826
20. M.P. Patricelli H.A. Lashuel D.K. Giang J.W. Kelly B.F. Cravatt Comparative characterization of a wild type and transmembrane domain-deleted fatty acid amide hydrolase: identification of the transmembrane domain as a site for oligomerization Biochemistry 37 1998 15177 15187
21. M. Mileni D.S. Johnson Z. Wang D.S. Everdeen M. Liimatta B. Pabst K. Bhattacharya R.A. Nugent S. Kamtekar B.F. Cravatt K. Ahn R.C. Stevens Structure-guided inhibitor design for human FAAH by interspecies active site conversion Proc. Natl. Acad. Sci. USA 105 2008 12820 12824
22. K. Ahn D.S. Johnson M. Mileni D. Beidler J.Z. Long M.K. McKinney E. Weerapana N. Sadagopan M. Liimatta S.E. Smith S. Lazerwith C. Stiff S. Kamtekar K. Bhattacharya Y. Zhang S. Swaney K. Van Becelaere R.C. Stevens B.F. Cravatt Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain Chem. Biol. 16 2009 411 420
23. M. Mileni J. Garfunkle J.K. DeMartino B.F. Cravatt D.L. Boger R.C. Stevens Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by alpha-ketoheterocycle inhibitors revealed from cocrystal structures J. Am. Chem. Soc. 131 2009 10497 10506
24. M. Mileni J. Garfunkle C. Ezzili F.S. Kimball B.F. Cravatt R.C. Stevens D.L. Boger X-ray crystallographic analysis of alpha-ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolase J. Med. Chem. 53 2010 230 240
25. M. Mileni S. Kamtekar D.C. Wood T.E. Benson B.F. Cravatt R.C. Stevens Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation J. Mol. Biol. 400 2010 743 754
26. X. Min S.T. Thibault A.C. Porter D.J. Gustin T.J. Carlson H. Xu M. Lindstrom G. Xu C. Uyeda Z. Ma Y. Li F. Kayser N.P. Walker Z. Wang Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH) Proc. Natl. Acad. Sci. USA 108 2011 7379 7384
27. M.K. McKinney B.F. Cravatt Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolase J. Biol. Chem. 278 2003 37393 37399
28. C.R. Guimaraes D.L. Boger W.L. Jorgensen Elucidation of fatty acid amide hydrolase inhibition by potent alpha-ketoheterocycle derivatives from Monte Carlo simulations J. Am. Chem. Soc. 127 2005 17377 17384
29. A. Lodola M. Mor J.C. Hermann G. Tarzia D. Piomelli A.J. Mulholland QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation Chem. Commun. (Camb) 2005 4399 4401
30. A. Lodola M. Mor J. Zurek G. Tarzia D. Piomelli J.N. Harvey A.J. Mulholland Conformational effects in enzyme catalysis: reaction via a high energy conformation in fatty acid amide hydrolase Biophys. J. 15 2006 L20 L22
31. A. Lodola J. Sirirak N. Fey S. Rivara M. Mor A.J. Mulholland Structural fluctuations in enzyme-catalyzed reactions: determinants of reactivity in fatty acid amide hydrolase from multivariate statistical analysis of quantum mechanics/molecular mechanics paths J. Chem. Theory Comput. 6 2010 2948 2960
32. I. Tubert-Brohman O. Acevedo W.L. Jorgensen Elucidation of hydrolysis mechanisms for fatty acid amide hydrolase and its Lys142Ala variant via QM/MM simulations J. Am. Chem. Soc. 128 2006 16904 16913
33. M. Seierstad J.G. Breitenbucher Discovery and development of fatty acid amide hydrolase (FAAH) inhibitors J. Med. Chem. 51 2008 7327 7343
34. C. Ezzili M. Mileni N. McGlinchey J.Z. Long S.G. Kinsey D.G. Hochstatter R.C. Stevens A.H. Lichtman B.F. Cravatt E.J. Bilsky D.L. Boger Reversible competitive alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics J. Med. Chem. 54 2011 2805 2822
35. S. Kathuria S. Gaetani D. Fegley F. Valino A. Duranti A. Tontini M. Mor G. Tarzia G. La Rana A. Calignano A. Giustino M. Tattoli M. Palmery V. Cuomo D. Piomelli Modulation of anxiety through blockade of anandamide hydrolysis Nat. Med. 9 2003 76 81
36. G. Tarzia A. Duranti A. Tontini G. Piersanti M. Mor S. Rivara P.V. Plazzi C. Park S. Kathuria D. Piomelli Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors J. Med. Chem. 46 2003 2352 2360
37. M. Mor S. Rivara A. Lodola P.V. Plazzi G. Tarzia A. Duranti A. Tontini G. Piersanti S. Kathuria D. Piomelli Cyclohexylcarbamic acid 3'-or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies J. Med. Chem. 47 2004 4998 5008
38. J.R. Clapper G. Moreno-Sanz R. Russo A. Guijarro F. Vacondio A. Duranti A. Tontini S. Sanchini N.R. Sciolino J.M. Spradley A.G. Hohmann A. Calignano M. Mor G. Tarzia D. Piomelli Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism Nat. Neurosci. 13 2010 1265 1270
39. A. Lodola L. Capoferri S. Rivara E. Chudyk J. Sirirak E. Dyguda-Kazimierowicz W. Andrzej Sokalski M. Mileni G. Tarzia D. Piomelli M. Mor A.J. Mulholland Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling Chem. Commun. (Camb) 47 2011 2517 2519
40. A. Lodola M. Mor S. Rivara C. Christov G. Tarzia D. Piomelli A.J. Mulholland Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling Chem. Commun. (Camb) 2008 214 216
41. J.M. Keith R. Apodaca W. Xiao M. Seierstad K. Pattabiraman J. Wu M. Webb M.J. Karbarz S. Brown S. Wilson B. Scott C.S. Tham L. Luo J. Palmer M. Wennerholm S. Chaplan J.G. Breitenbucher Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase Bioorg. Med. Chem. Lett. 18 2008 4343 4838
42. K. Ahn D.S. Johnson L.R. Fitzgerald M. Liimatta A. Arendse T. Stevenson E.T. Lund R.A. Nugent T.K. Nomanbhoy J.P. Alexander B.F. Cravatt Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity Biochemistry 46 2007 13019 13030
43. M.K. McKinney B.F. Cravatt Structure and function of fatty acid amide hydrolase Annu. Rev. Biochem 74 2005 411 432
44. K. Ahn D.S. Johnson B.F. Cravatt Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders Expert Opin. Drug. Discov. 4 2009 763 784
45. G. Mei A. Di Venere V. Gasperi E. Nicolai K.R. Masuda A. Finazzi-Agro B.F. Cravatt M. Maccarrone Closing the gate to the active site: effect of the inhibitor methoxyarachidonyl fluorophosphonate on the conformation and membrane binding of fatty acid amide hydrolase J. Biol. Chem. 282 2007 3829 3836
46. C. Moller M.S. Plesset Note on an approximation treatment for many-electron systems Phys. Rev. 46 1934 0618 0622
47. P. Hohenberg W. Kohn In homogeneous electron gas Phys. Rev. B 136 1964 B864
48. W. Kohn L.J. Sham Self-consistent equations including exchange and correlation effects Phys. Rev. 140 1965 1133
49. A.D. Becke Density-functional exchange-energy approximation with correct asymptotic-behavior Phys. Rev. A 38 1988 3098 3100
50. C.T. Lee W.T. Yang R.G. Parr Development of the Colle-Salvetti correlation-energy formula into a functional of the electron-density Phys. Rev. B 37 1988 785 789
51. A.D. Becke A new mixing of Hartree-Fock and local density-functional theories J. Chem. Phys. 98 1993 1372 1377
52. S.H. Vosko L. Wilk M. Nusair Accurate spin-dependent electron liquid correlation energies for local spin-density calculations-a critical analysis Can. J. Phys. 58 1980 1200 1211
53. P. Carloni U. Rothlisberger M. Parrinello The role and perspective of ab initio molecular dynamics in the study of biological systems Acc. Chem. Res. 35 2002 455 464
54. U. Rothlisberger P. Carloni Drug-target binding investigated by quantum mechanical/molecular mechanical (QM/MM) Methods. Lect. Notes Phys. 704 2006 449 479
55. Y. Zhao D.G. Truhlar Density functionals with broad applicability in chemistry Acc. Chem. Res. 41 2008 157 167
56. Y. Zhao D.G. Truhlar The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals Theor. Chem. Acc. 120 2008 215 241
57. R. Car M. Parrinello Unified approach for molecular-dynamics and density-functional theory Phys. Rev. Lett. 55 1985 2471 2474
58. E. Brunk N. Ashari P. Athri P. Campomanes F.F. de Carvalho B.F.E. Curchod P. Diamantis M. Doemer J. Garrec A. Laktionov M. Micciarelli M. Neri G. Palermo T.J. Penfold S. Vanni I. Tavernelli U. Rothlisberger Pushing the frontiers of first-principles based computer simulations of chemical and biological systems Chimia 65 2011 667 671
59. M. Dal Peraro A.J. Vila P. Carloni M.L. Klein Role of zinc content on the catalytic efficiency of B1 metallo beta-lactamases J. Am. Chem. Soc. 129 2007 2808 2816
60. M. De Vivo M. Dal Peraro M.L. Klein Phosphodiester cleavage in ribonuclease H occurs via an associative two-metal-aided catalytic mechanism J. Am. Chem. Soc. 130 2008 10955 10962
61. M. De Vivo B. Ensing M. Dal Peraro G.A. Gomez D.W. Christianson M.L. Klein Proton shuttles and phosphatase activity in soluble epoxide hydrolase J. Am. Chem. Soc. 129 2007 387 394
62. M. De Vivo B. Ensing M.L. Klein Computational study of phosphatase activity in soluble epoxyde hydrolase: high efficiency through a water bridge mediated proton shuttle J. Am. Chem. Soc. 127 32 2005 11226 11227
63. M.J.S. Dewar W. Thiel Ground-states of molecules. 38. Mndo method-approximations and parameters J. Am. Chem. Soc. 99 1977 4899 4907
64. M.J.S. Dewar D.M. Storch The development and use of quantum molecular-models. 75. Comparative tests of theoretical procedures for studying chemical-reactions J. Am. Chem. Soc. 107 1985 3898 3902
65. J.J.P. Stewart Optimization of parameters for semiempirical methods.1 Method. J. Comput. Chem. 10 1989 209 220
66. M.P. Repasky J. Chandrasekhar W.L. Jorgensen PDDG/PM3 and PDDG/MNDO: Improved semiempirical methods J. Comput. Chem. 23 2002 1601 1622
67. B.J. Alder T.E. Wainwright Phase transition for a hard sphere system J. Chem. Phys. 27 1957 1208 1209
68. E. Fermi J.G. Pasta S.M. Ulam Los Alamos LASL Report 1955
69. A. Rahman Correlations in the motion of atoms in liquid argon Phys. Rev. A 136 1964 405 411
70. M.P. Allen D.J. Tildesley Computer Simulation of Liquids second ed. 1994 Oxford University Press Oxford
71. D. Frenkel B. Smit Understanding Molecular Simulation second ed. 2002 Academic Press San Diego
72. W.L. Jorgensen D.S. Maxwell J. Tirado-Rives Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids J. Am. Chem. Soc. 118 1996 11225 11236
73. Y. Duan C. Wu S. Chowdhury M.C. Lee G. Xiong W. Zhang R. Yang P. Cieplak R. Luo T. Lee J. Caldwell J. Wang P. Kollman A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations J. Comput. Chem. 24 2003 1999 2012
74. M. Christen P.H. Hunenberger D. Bakowies R. Baron R. Burgi D.P. Geerke T.N. Heinz M.A. Kastenholz V. Krautler C. Oostenbrink C. Peter D. Trzesniak W.F. van Gunsteren The GROMOS software for biomolecular simulation: GROMOS05 J. Comput. Chem. 26 2005 1719 1751
75. A.D. MacKerell D.J. Bashford M. Bellott R.L. Dunbrack D.J.J. Evanseck J.M. Field S. Fischer J. Gao H. Guo S. Ha D. Joseph-McCarthy L. Kuchnir K. Kuczera K.T.F. Lau C. Mattos S. Michnick T. Ngo D.T. Nguyen B. Prodhom E.W. Reiher B.I. Roux M. Schlenkrich J.C. Smith R. Stote J. Straub M. Watanabe J. Wiorkiewicz-Kuczera D. Yin M. Karplus All-Atom empirical potential for molecular modeling and dynamics studies of proteins Phys. Chem. B 102 1998 3586 3616
76. J. Wang R.M. Wolf J.W. Caldwell P.A. Kollman D.A. Case Development and testing of a general amber force field J. Comput. Chem. 25 2004 1157 1174
77. K. Vanommeslaeghe E. Hatcher C. Acharya S. Kundu S. Zhong J. Shim E. Darian O. Guvench P. Lopes I. Vorobyov A.D. Mackerell Jr. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields J. Comput. Chem. 31 2010 671 690
78. M. De Vivo A. Cavalli G. Bottegoni P. Carloni M. Recanatini Role of phosphorylated Thr160 for the activation of the CDK2/Cyclin a complex Proteins Struct. Funct. Bioinform. 62 2006 89 98
79. M. De Vivo G. Bottegoni A. Berteotti M. Recanatini F.L. Gervasio A. Cavalli Cyclin-dependent kinases: bridging their structure and function through computations Future Med. Chem. 3 2011 1551 1559
80. A. Laio M. Parrinello Escaping free-energy minima Proc. Natl. Acad. Sci. USA 99 2002 12562 12566
81. B. Ensing M. De Vivo Z.W. Liu P. Moore M.L. Klein Metadynamics as a tool for exploring free energy landscapes of chemical reactions Acc. Chem. Res. 39 2006 73 81
82. W.L. Jorgensen Efficient drug lead discovery and optimization Acc. Chem. Res. 42 2009 724 733
83. W.L. Jorgensen L.L. Thomas Perspective on free-energy perturbation calculations for chemical equilibria J. Chem. Theory Comput. 4 2004 869 876
84. I. Bisha A. Laio A. Magistrato A. Giorgetti J. Sgrignani A candidate ion-retaining state in the inward-facing conformation of sodium/galactose symporter: clues from atomistic simulations J. Chem. Theory Comput. 9 2013 1240 1246
85. A. Warshel M. Levitt Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme J. Mol. Biol. 103 1976 227 249
86. R.A. Friesner V. Guallar Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic catalysis Annu. Rev. Phys. Chem. 56 2005 389 427
87. H.M. Senn W. Thiel QM/MM methods for biomolecular systems Angew. Chem. Int. Ed. Engl. 48 2009 1198 1229
88. A. Warshel Computer simulations of enzyme catalysis: methods, progress, and insights Ann. Rev. Biophys. Biomolec. Struct. 32 2003 425 443
89. J.L. Gao Hybrid quantum and molecular mechanical simulations: an alternative avenue to solvent effects in organic chemistry Acc. Chem. Res. 29 1996 298 305
90. A. Cavalli P. Carloni M. Recanatini Target-related applications of first principles quantum chemical methods in drug design Chem. Rev. 106 2006 3497 3519
91. M. Dal Peraro P. Ruggerone S. Raugei F.L. Gervasio P. Carloni Investigating biological systems using first principles Car-Parrinello molecular dynamics simulations Curr. Opin. Struct. Biol. 17 2007 149 156
92. T. Vreven K.S. Byun I. Komaromi S. Dapprich J.A. Montgomery K. Morokuma M.J. Frisch Combining quantum mechanics methods with molecular mechanics methods in ONIOM J. Chem. Theory. Comput. 2 2006 815 826
93. G.W. Trucks H.B. Schlegel G.E. Scuseria M.A. Robb J.R. Cheeseman G. Scalmani V. Barone B. Mennucci G.A. Petersson H. Nakatsuji M. Caricato X. Li H.P. Hratchian A.F. Izmaylov J. Bloino G. Zheng J.L. Sonnenberg M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. J.A. Montgomery Jr. J.E. Peralta F. Ogliaro M. Bearpark J.J. Heyd E. Brothers K.N. Kudin V.N. Staroverov R. Kobayashi J. Normand K. Raghavachari A. Rendell J.C. Burant S.S. Iyengar J. Tomasi M. Cossi N. Rega J.M. Millam M. Klene J.E. Knox J.B. Cross V. Bakken C. Adamo J. Jaramillo R. Gomperts R.E. Stratmann O. Yazyev A.J. Austin R. Cammi C. Pomelli J.W. Ochterski R.L. Martin K. Morokuma V.G. Zakrzewski G.A. Voth P. Salvador J.J. Dannenberg S. Dapprich A.D. Daniels Ö. Farkas J.B. Foresman J.V. Ortiz J. Cioslowski D.J. Fox Gaussian 09, M. J. F. 2009 Gaussian, Inc Wallingford CT
94. A. Laio J. VandeVondele U. Rothlisberger D-RESP: dynamically generated electrostatic potential derived charges from quantum mechanics/molecular mechanics simulations J. Phys. Chem. B 106 2002 7300 7307
95. A. Laio J. VandeVondele U. Rothlisberger A Hamiltonian electrostatic coupling scheme for hybrid Car-Parrinello molecular dynamics simulations J. Chem. Phys. 116 2002 6941 6947
96. T. Laino F. Mohamed A. Laio M. Parrinello An efficient real space multigrid OM/MM electrostatic coupling J. Chem. Theory. Comput. 1 2005 1176 1184
97. R.A. Friesner Combined quantum and molecular mechanics (QM/MM) Drug. Discov. Today: Technol. 1 2004 253 260
98. M.P. Gleeson D. Gleeson QM/MM calculations in drug discovery: a useful method for studying binding Phenomena? J. Chem. Inf. Model 49 2009 670 677
99. M.P. Gleeson D. Gleeson QM/MM as a tool in fragment based drug discovery. A cross-docking, rescoring study of kinase inhibitors J. Chem. Inf. Model 49 2009 1437 1448
100. A. Lodola M. De Vivo The increasing role of QM/MM in drug discovery Adv. Protein Chem. Struct. Biol. 87 2012 337 362
101. M. De Vivo Bridging quantum mechanics and structure-based drug design Front. Biosci. Landmrk 16 2011 1619 1633
102. A. Lodola D. Branduardi M. De Vivo L. Capoferri M. Mor D. Piomelli A. Cavalli A catalytic mechanism for cysteine N-terminal nucleophile hydrolases, as revealed by free energy simulations PLoS One 7 2012 e32397
103. F. Claeyssens J.N. Harvey F.R. Manby R.A. Mata A.J. Mulholland K.E. Ranaghan M. Schutz S. Thiel W. Thiel H.J. Werner High-accuracy computation of reaction barriers in enzymes Angew. Chem. Int. Ed. Engl. 45 2006 6856 6859
104. A.J. Mulholland Computational enzymology: modelling the mechanisms of biological catalysts Biochem. Soc. Trans. 36 2008 22 26
105. E. Rosta M. Klahn A. Warshel Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions J. Phys. Chem. B 110 2006 2934 2941
106. M.H. Ho M. De Vivo M. Dal Peraro M.L. Klein Unraveling the catalytic pathway of metalloenzyme farnesyltransferase through QM/MM computation J. Chem. Theory Comput. 5 2009 1657 1666
107. G. Palermo M. Stenta A. Cavalli M. Dal Peraro M. De Vivo Molecular simulations highlight the role of metals in catalysis and inhibition of type II topoisomerase J. Chem. Theory Comput. 9 2013 857 862
108. A.E. Cho V. Guallar B.J. Berne R. Friesner Importance of accurate charges in molecular docking: quantum mechanical/molecular mechanical (QM/MM) approach Comput. Chem. 26 2005 915 931
109. A. Khandelwal V. Lukacova D. Comez D.M. Kroll S. Raha S. Balaz A combination of docking, QM/MM methods, and MD simulation for binding affinity estimation of metalloprotein ligands J. Med. Chem. 48 2005 5437 5447
110. T. Sander T. Lijefors T. Balle Prediction of the receptor conformation for iGluR2 agonist binding: QM/MM docking to an extensive conformational ensemble generated using normal mode analysis J. Mol. Graph. Model 26 2008 1259 1268
111. M. Kaukonen P. Soderhjelm J. Heimdal U. Ryde QM/MM-PBSA method to estimate free energies for reactions in proteins J. Phys. Chem. B 112 2008 12537 12548
112. A. Khandelwal S. Balaz QM/MM linear response method distinguishes ligand affinities for closely related metalloproteins Protein-Struct. Funct. Bioinforma. 69 2007 326 339
113. D.L. Boger H. Miyauchi W. Du C. Hardouin R.A. Fecik H. Cheng I. Hwang M.P. Hedrick D. Leung O. Acevedo C.R. Guimaraes W.L. Jorgensen B.F. Cravatt Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics J. Med. Chem. 48 2005 1849 1856
114. L. Capoferri M. Mor J. Sirirak E. Chudyk A.J. Mulholland A. Lodola Application of a SCC-DFTB QM/MM approach to the investigation of the catalytic mechanism of fatty acid amide hydrolase J. Mol. Model 17 2011 2375 2383
115. A. Lodola M. Mor J. Sirirak A.J. Mulholland Insights into the mechanism and inhibition of fatty acid amide hydrolase from quantum mechanics/molecular mechanics (QM/MM) modelling Biochem. Soc. Trans. 37 2009 363 367
116. J. Gao S. Ma D.T. Major K. Nam J. Pu D.G. Truhlar Mechanisms and free energies of enzymatic reactions Chem. Rev. 16 2006 3188 3209
117. O. Acevedo W.L. Jorgensen Advances in quantum and molecular mechanical (QM/MM) simulations for organic and enzymatic reactions Acc. Chem. Res. 43 2010 142 151
118. A. Lodola L. Capoferri S. Rivara G. Tarzia D. Piomelli A. Mulholland M. Mor Quantum mechanics/molecular mechanics modeling of fatty acid amide hydrolase reactivation distinguishes substrate from irreversible covalent inhibitors J. Med. Chem. 56 2013 2500 2512
119. G. Palermo P. Campomanes M. Neri D. Piomelli A. Cavalli U. Rothlisberger M. De Vivo Wagging the tail: essential role of substrate flexibility in FAAH catalysis J. Chem. Theory Comput. 9 2013 1202 1213
120. G. Palermo D. Branduardi M. Masetti A. Lodola M. Mor D. Piomelli A. Cavalli M. De Vivo Covalent inhibitors of fatty acid amide hydrolase: a rationale for the activity of piperidine and piperazine aryl ureas J. Med. Chem. 54 2011 6612 6623
121. E. Dainese G. De Fabritiis A. Sabatucci S. Oddi C.B. Angelucci C. Di Pancrazio T. Giorgino N. Stanley M. Del Carlo B.F. Cravatt M. Maccarrone Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH Biochem. J. 457 2014 463 472
122. M.J. Karbarz L. Luo L. Chang C.S. Tham J.A. Palmer S.J. Wilson M.L. Wennerholm S.M. Brown B.P. Scott R.L. Apodaca J.M. Keith J. Wu J.G. Breitenbucher S.R. Chaplan M. Webb Biochemical and biological properties of 4-[3-phenyl-[1,2,4] thiadiazol-5-yl]-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase Anesth. Analgesia 108 2009 316 329
123. V. Hornak R. Abel A. Okur B. Strockbine A. Roitberg C. Simmerling Comparison of multiple Amber force fields and development of improved protein backbone parameters Proteins 65 2006 712 725
124. T. Vreven K. Morokuma O. Farkas H.B. Schlegel M.J. Frisch Geometry optimization with QM/MM, ONIOM, and other combined methods. I. Microiterations and constraints J. Comput. Chem. 24 2003 760 769