Structural fluctuations in enzyme-catalyzed reactions: Determinants of Reactivity in fatty acid amide hydrolase from multivariate statistical analysis of quantum mechanics/molecular mechanics paths

Journal of Chemical Theory and Computation

Volumn 6, Issue 9, 2010, Pages 2948-2960

  Lodola, Alessio ^a   Sirirak, Jitnapa ^b   Fey, Natalie ^b   Rivara, Silvia ^a   Mor, Marco ^a   Mulholland, Adrian J ^b  

^a UNIVERSITY OF PARMA   (Italy)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77956595530     PISSN: 15499618     EISSN: 15499626     Source Type: Journal    
DOI: 10.1021/ct100264j     Document Type: Article

References (64)

1. Karplus, M.; Gao, Y. Q.; Ma, J.; van der Vaart, A.; Yang, W. Protein Structural Transitions and Their Functional Role Philos. Trans. R. Soc. London, A 2005, 363, 331-355
2. Min, W.; English, B. P.; Luo, G.; Cherayil, B. J.; Kou, S. C.; Xie, X. S. Fluctuating Enzymes: Lessons from Single-Molecule Studies Acc. Chem. Res. 2005, 38, 923-931
3. Qian, H.; Shi, P. Z. When Does the Michaelis-Menten Equation Hold for Fluctuating Enzymes? J. Phys. Chem. B 2009, 113, 2225-2230
4. Gorfe, A. A.; Lu, B.; Yu, Z.; McCammon, J. A. Enzymatic Activity versus Structural Dynamics: The Case of Acetylcholinesterase Tetramer Biophys. J. 2009, 97, 897-905
5. Liu, Y. H.; Konermann, L. Conformational Dynamics of Free and Catalytically Active Thermolysin Are Indistinguishable by Hydrogen/Deuterium Exchange Mass Spectrometry Biochemistry 2008, 47, 6342-6351
6. Olsson, M. H.; Parson, W. W.; Warshel, A. Dynamical Contributions to Enzyme Catalysis: Critical Tests of a Popular Hypothesis Chem. Rev. 2006, 106, 1737-1756
7. Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations Science 2004, 303, 186-195
8. Olsson, M. H.; Mavri, J.; Warshel, A. Transition State Theory Can Be Used in Studies of Enzyme Catalysis: Lessons from Simulations of Tunnelling and Dynamical Effects in Lipoxygenase and Other Systems Philos. Trans. R. Soc. London, B 2006, 361, 1417-1432
9. Claeyssens, F.; Harvey, J. N.; Manby, F. R.; Mata, R. A.; Mulholland, A. J.; Ranaghan, K. E.; Schütz, M.; Thiel, S.; Thiel, W.; Werner, H. J. High-Accuracy Computation of Reaction Barriers in Enzymes Angew. Chem., Int. Ed. 2006, 45, 6856-6859
10. Honkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Nørskov, J. K. Ammonia Synthesis from First-Principles Calculations Science 2005, 307, 555-558
11. Pentikâinen, U.; Pentikâinen, O. T.; Mulholland, A. J. Cooperative Symmetric to Asymmetric Conformational Transition of the Apo-Form of Scavenger Decapping Enzyme Revealed by Simulations Proteins 2008, 70, 498-508
12. Thorpe, I. F.; Brooks, C. L. Conformational Substates Modulate Hydride Transfer in Dihydrofolate Reductase J. Am. Chem. Soc. 2005, 127, 12997-13006
13. Karplus, M.; McCammon, J. A. Dynamics of Proteins: Elements and Function Annu. Rev. Biochem. 1983, 53, 263-300
14. Villà, J.; Warshel, A. Energetics and Dynamics of Enzymatic Reactions J. Phys. Chem. B 2001, 105, 7887-7907
15. Lodola, A.; Mor, M.; Zurek, J.; Tarzia, G.; Piomelli, D.; Harvey, J. N.; Mulholland, A. J. Conformational Effects in Enzyme Catalysis: Reaction via a High Energy Conformation in Fatty Acid Amide Hydrolase Biophys. J. 2007, 92, L20-L22
16. van der Kamp, M. W.; Mulholland, A. J. Computational Enzymology: Insight into Biological Catalysts from Modeling Nat. Prod. Rep. 2008, 25, 1001-1014
17. Cavalli, A.; Carloni, P.; Recanatini, M. Target-Related Applications of First Principles Quantum Chemical Methods in Drug Design Chem. Rev. 2006, 106, 3497-3519
18. Karplus, M.; McCammon, J. A. Molecular Dynamics Simulations of Biomolecules Nat. Struct. Biol. 2002, 9, 646-652
19. Senn, H. D.; Thiel, W. QM/MM Studies of Enzymes Curr. Opin. Chem. Biol. 2007, 11, 182-187
20. Warshel, A. Computer Simulations of Enzyme Catalysis: Methods, Progress, and Insights Annu. Rev. Biophys. Biomol. Struct. 2003, 32, 425-443
21. Friesner, R. A.; Guallar, V. Ab Initio Quantum Chemical and Mixed Quantum Mechanics/Molecular Mechanics (QM/MM) Methods for Studying Enzymatic Catalysis Annu. Rev. Phys. Chem. 2005, 56, 389-427
22. Field, M. J.; Bash, P. A.; Karplus, M. A Combined Quantum Mechanical and Molecular Mechanical Potential for Molecular Dynamics Simulations J. Comput. Chem. 1990, 11, 700-733
23. Senn, H. M.; Thiel, W. QM/MM Methods for Biomolecular Systems Angew. Chem., Int. Ed. 2009, 48, 1198-1229
24. Mulholland, A. J. Computational Enzymology: Modelling the Mechanisms of Biological Catalysts Biochem. Soc. Trans. 2008, 36, 22-26
25. Hu, H.; Yang, W. Free Energies of Chemical Reactions in Solution and in Enzymes with ab Initio Quantum Mechanics/Molecular Mechanics Methods Annu. Rev. Phys. Chem. 2008, 59, 573-601
26. Mulholland, A. J. The QM/MM Approach to Enzymatic Reactions. In Theoretical Biochemistry; Eriksson, L. A., Ed.; Elsevier: Amsterdam, 2001; pp 597 - 653.
27. Cui, Q.; Karplus, M. Quantum Mechanical/Molecular Mechanical Studies of the Triosephosphate Isomerase-Catalyzed Reaction: Verification of Methodology and Analysis of Reaction Mechanisms J. Phys. Chem. B 2002, 106, 1678-1698
28. Lodola, A.; Woods, C. J.; Mulholland, A. J. Applications and Advances of QM/MM Methods in Computational Enzymology. In Annual Reports in Computational Chemistry; Wheeler, R. A.; Spellmeyer, D. C., Eds.; Elsevier: Amsterdam, 2008; Vol. 4, Chapter 9, pp 155 - 169.
29. Kamerlin, S. C.; Haranczyk, M.; Warshel, A. Progress in ab Initio QM/MM Free-Energy Simulations of Electrostatic Energies in Proteins: Accelerated QM/MM Studies of pKa, Redox Reactions and Solvation Free Energies J. Phys. Chem. B 2009, 113, 1253-272
30. Bowman, A. L.; Ridder, L.; Rietjens, I. M.; Vervoort, J.; Mulholland, A. J. Molecular Determinants of Xenobiotic Metabolism: QM/MM Simulation of the Conversion of 1-Chloro-2,4-dinitrobenzene Catalyzed by M1-1 Glutathione S-Transferase Biochemistry 2007, 46, 6353-6363
31. Klâhn, M.; Braun-Sand, S.; Rosta, E.; Warshel, A. On Possible Pitfalls in ab Initio Quantum Mechanics/Molecular Mechanics Minimization Approaches for Studies of Enzymatic Reactions J. Phys. Chem. B 2005, 109, 15645-15650
32. Zhang, Y.; Kua, J.; McCammon, J. A. Influence of Structural Fluctuation on Enzyme Reaction Energy Barriers in Combined Quantum Mechanical/Molecular Mechanical Studies J. Phys. Chem. B 2003, 107, 4459-4463
33. Piomelli, D. The Molecular Logic of Endocannabinoid Signalling Nat. Rev. Neurosci. 2003, 4, 873-884
34. Lodola, A.; Mor, M.; Hermann, J. C.; Tarzia, G.; Piomelli, D.; Mulholland, A. J. QM/MM Modelling of Oleamide Hydrolysis in Fatty Acid Amide Hydrolase (FAAH) Reveals a New Mechanism of Nucleophile Activation Chem. Commun. 2005, 439, 9-4401
35. Tubert-Brohman, I.; Acevedo, O.; Jorgensen, W. L. Elucidation of Hydrolysis Mechanisms for Fatty Acid Amide Hydrolase and Its Lys142Ala Variant via QM/MM Simulations J. Am. Chem. Soc. 2006, 128, 16904-16913
36. McKinney, M. K.; Cravatt, B. F. Evidence for Distinct Roles in Catalysis for Residues of the Serine-Serine-Lysine Catalytic Triad of Fatty Acid Amide Hydrolase J. Biol. Chem. 2003, 278, 37393-37399
37. Stewart, J. J. P. Optimization of Parameters for Semiempirical Methods. 2. Applications J. Comput. Chem. 1989, 10, 221-264
38. MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins J. Phys. Chem. A 1998, 102, 3586-3616
39. Lonsdale, R.; Ranaghan, K. E.; Mulholland, A. J. Computational Enzymology Chem. Commun. 2010, 2354-2372
40. Hermann, J. C.; Ridder, L.; Mulholland, A. J.; Hôltje, H. D. Identification of Glu166 as the General Base in the Acylation Reaction of Class A β-Lactamases through QM/MM Modeling J. Am. Chem. Soc. 2003, 125, 9590-9591
41. Ridder, L.; Mulholland, A. J.; Vervoort, J.; Rietjens, I. M. C. M. Correlation of Calculated Activation Energies with Experimental Rate Constants for an Enzyme Catalyzed Aromatic Hydroxylation J. Am. Chem. Soc. 1998, 120, 7641-7642
42. Wold, S.; Esbensen, K.; Geladi, P. Principal Component Analysis Chemom. Intell. Lab. Syst. 1987, 2, 37-52
43. Wold, S.; Sjostrom, M.; Eriksson, L. PLS-Regression: A Basic Tool of Chemometrics Chemom. Intell. Lab. Syst. 2001, 58, 109-130
44. Wold, S.; Ruhe, A.; Wold, H.; Dunn, W. J. The Collinearity Problem in Linear Regression. The Partial Least Squares (PLS) Approach to Generalized Inverses SIAM J. Sci. Stat. Comput. 1984, 5, 735-743
45. Draper, N. R.; Smith, H. Applied Regression Analysis, 2 nd ed.; Wiley: New York, 1980.
46. Eriksson, L.; Johansson, E.; Kettaneh-Wold, N.; Trygg, J.; Wikstrom, C.; Wold, S. Multi- and MegaVariate Data Analysis - Basic Principles and Applications, 2 nd ed.; Umetrics AB: Umé, Sweden, 2006.
47. Mor, M.; Rivara, S.; Lodola, A.; Plazzi, P. V.; Tarzia, G.; Duranti, A.; Tontini, A.; Piersanti, G.; Kathuria, S.; Piomelli, D. 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. 2004, 47, 4998-5008
48. Mor, M.; Lodola, A.; Rivara, S.; Vacondio, F.; Duranti, A.; Tontini, A.; Sanchini, S.; Piersanti, G.; Clapper, J. R.; King, A. R.; Tarzia, G.; Piomelli, D. Synthesis and Quantitative Structure-Activity Relationship of Fatty Acid Amide Hydrolase Inhibitors: Modulation at the N-Portion of Biphenyl-3-yl Alkylcarbamates J. Med. Chem. 2008, 51, 3487-3498
49. Valitutti, G.; Duranti, A.; Lodola, A.; Mor, M.; Piersanti, G.; Piomelli, D.; Rivara, S.; Tontini, A.; Tarzia, G.; Traldi, P. Correlation between Energetics of Collisionally Activated Decompositions, Interaction Energy and Biological Potency of Carbamate FAAH Inhibitors J. Mass Spectrom. 2007, 42, 1624-1627
50. Tantanak, D.; Limtrakul, J.; Gleeson, M. P. Probing the Structural and Electronic Factors Affecting the Adsorption and Reactivity of Alkenes in Acidic Zeolites Using DFT Calculations and Multivariate Statistical Methods J. Chem. Inf. Model. 2005, 45, 1303-1312
51. Gleeson, D. Application of QM Simulations and Multivariate Analysis in the Study of Alkene Reactivity in the Zeolite H-ZSM5 J. Chemom. 2008, 22, 372-377
52. Fey, N.; Guy Orpen, A.; Harvey, J. N. Building Ligand Knowledge Bases for Organometallic Chemistry: Computational Description of Phosphorus(III)-Donor Ligands and the Metal-Phosphorus Bond Coord. Chem. Rev. 2009, 253, 704-722
53. Chatfield, C.; Collins, A. J. Introduction to Multivariate Analysis; Chapman and Hall: London, 1980.
54. Box, G. E. P.; Hunter, W. G.; Hunter, J. S. Statistics for Experimenters; Wiley: New York, 1978.
55. Cramer, R. D., III.; Bunce, J. D.; Patterson, D. E. Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies Quant. Struct.-Act. Relat. 1988, 7, 18-25
56. SIMCA-P+, version 11.0; Umetrics AB: Umé, Sweden, 2005.
57. Bracey, M. H.; Hanson, M. A.; Masuda, K. R.; Stevens, R. C.; Cravatt, B. F. Structural Adaptation in a Membrane Enzyme That Terminates Endocannabinoid Signaling Science 2002, 298, 1793-1796
58. Lodola, A.; Mor, M.; Sirirak, J.; Mulholland, A. J. Insights into the Mechanism and Inhibition of Fatty Acid Amide Hydrolase from Quantum Mechanics/Molecular Mechanics (QM/MM) Modeling Biochem. Soc. Trans. 2009, 37, 363-367
59. Acevedo, O.; Jorgensen, W. L. Advances in Quantum and Molecular Mechanical (QM/MM) Simulations for Organic and Enzymatic Reactions Acc. Chem. Res. 2010, 43, 142-151
60. Patricelli, M. P.; Cravatt, B. F. Clarifying the Catalytic Roles of Conserved Residues in the Amidase Signature Family J. Biol. Chem. 2000, 275, 19177-18184
61. Lodola, A.; Mor, M.; Rivara, S.; Christov, C.; Tarzia, G.; Piomelli, D.; Mulholland, A. J. Identification of Productive Inhibitor Binding Orientation in Fatty Acid Amide Hydrolase (FAAH) by QM/MM Mechanistic Modelling Chem. Commun. 2008, 214-216
62. McKinney, M. K.; Cravatt, B. F. Structure and Function of Fatty Acid Amide Hydrolase Annu. Rev. Biochem. 2005, 74, 411-432
63. Hotellings ellipsoids are equidensity contours resulting from multivariate normal distributions. They describe the area in which an observation can be expected to fall with a certain probability (e.g., 95%).
64. Mansson, R. A.; Welsh, A. H.; Fey, N.; Orpen, A. G. Statistical Modeling of a Ligand Knowledge Base J. Chem. Inf. Model. 2006, 46, 2591-2600