Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

Journal of Chemical Physics

Volumn 144, Issue 18, 2016, Pages

  Warshel, Arieh ^a   Bora, Ram Prasad ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYMES; SEMANTICS;

CHEMICAL PHYSICS; CONFORMATIONAL DYNAMICS; CRITICAL REVIEW; DYNAMICAL EFFECTS; ENZYME CATALYSIS; RELEVANT REACTIONS; SCIENTIFIC HYPOTHESIS; THEORETICAL STUDY;

CATALYSIS;

ENZYME;

BIOCATALYSIS; CHEMICAL MODEL; CHEMISTRY; COMPUTER SIMULATION; MOLECULAR MODEL; PROTEIN CONFORMATION; THERMODYNAMICS;

BIOCATALYSIS; COMPUTER SIMULATION; ENZYMES; MODELS, CHEMICAL; MODELS, MOLECULAR; PROTEIN CONFORMATION; THERMODYNAMICS;

EID: 84971264954     PISSN: 00219606     EISSN: None     Source Type: Journal    
DOI: 10.1063/1.4947037     Document Type: Article

References (184)

1. M. H. Olsson, W. W. Parson, and A. Warshel, " Dynamical contributions to enzyme catalysis: Critical tests of a popular hypothesis," Chem. Rev. 106, 1737-1756 (2006). 10.1021/cr040427e
2. S. C. L. Kamerlin and A. Warshel, " At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?," Proteins: Struct., Funct., Bioinf. 78, 1339-1375 (2010). 10.1002/prot.22654
3. A. Warshel, " Energetics of enzyme catalysis," Proc. Natl. Acad. Sci. U. S. A. 75, 5250-5254 (1978). 10.1073/pnas.75.11.5250
4. A. Warshel, P. K. Sharma, M. Kato, Y. Xiang, H. Liu, and M. H. M. Olsson, " Electrostatic basis for enzyme catalysis," Chem. Rev. 106, 3210-3235 (2006). 10.1021/cr0503106
5. A. T. P. Carvalho, F. Duarte, K. Vavitsas, and S. C. L. Kamerlin, Conformational and Chemical Landscapes of Enzyme Catalysis (CRC Press, 2015).
6. G. Careri, P. Fasella, and E. Gratton, " Enzyme dynamics: The statistical physics approach," Annu. Rev. Biophys. Bioeng. 8, 69-97 (1979). 10.1146/annurev.bb.08.060179.000441
7. B. Gavish and M. M. Werber, " Viscosity-dependent structural fluctuation in enzyme catalysis," Biochemistry 18, 1269-1275 (1979). 10.1021/bi00574a023
8. J. A. McCammon, P. G. Wolynes, and M. Karplus, " Picosecond dynamics of tyrosine side chains in proteins," Biochemistry 18, 927-942 (1979). 10.1021/bi00573a001
9. M. Karplus and J. A. McCammon, " Dynamics of proteins: Elements and function," Annu. Rev. Biochem. 52, 263-300 (1983). 10.1146/annurev.bi.52.070183.001403
10. W. R. Cannon, S. F. Singleton, and S. J. Benkovic, " A perspective on biological catalysis," Nat. Struct. Biol. 3, 821-833 (1996). 10.1038/nsb1096-821
11. E. Neria and M. Karplus, " Molecular dynamics of an enzyme reaction: Proton transfer in TIM," Chem. Phys. Lett. 267, 23-30 (1997). 10.1016/S0009-2614(97)00068-7
12. D. Antoniou and S. D. Schwartz, " Large kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations," Proc. Natl. Acad. Sci. U. S. A. 94, 12360-12365 (1997). 10.1073/pnas.94.23.12360
13. G. P. Miller and S. J. Benkovic, " Deletion of a highly motional residue affects formation of the Michaelis complex for Escherichia coli dihydrofolate reductase," Biochemistry 37, 6327-6335 (1998). 10.1021/bi972922t
14. P. Zavodszky, J. Kardos, A. Svingor, and G. A. Petsko, " Adjustment of conformational flexibility is a key event in the thermal adaptation of proteins," Proc. Natl. Acad. Sci. U. S. A. 95, 7406-7411 (1998). 10.1073/pnas.95.13.7406
15. A. Kohen, R. Cannio, S. Bartolucci, and J. P. Klinman, " Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase," Nature 399, 496-499 (1999). 10.1038/20981
16. A. Kohen and J. P. Klinman, " Hydrogen tunneling in biology," Chem. Biol. 6, R191-R198 (1999). 10.1016/S1074-5521(99)80058-1
17. X. S. Xie and H. P. Lu, " Single-molecule enzymology," J. Biol. Chem. 274, 15967-15970 (1999). 10.1074/jbc.274.23.15967
18. J. Basran, M. J. Sutcliffe, and N. S. Scrutton, " Enzymatic H-transfer requires vibration-driven extreme tunneling," Biochemistry 38, 3218-3222 (1999). 10.1021/bi982719d
19. J. L. Radkiewicz and C. L. Brooks, " Protein dynamics in enzymatic catalysis: Exploration of dihydrofolate reductase," J. Am. Chem. Soc. 122, 225-231 (2000). 10.1021/ja9913838
20. E. Z. Eisenmesser, D. A. Bosco, M. Akke, and D. Kern, " Enzyme dynamics during catalysis," Science 295, 1520-1523 (2002). 10.1126/science.1066176
21. R. M. Daniel, R. V. Dunn, J. L. Finney, and J. C. Smith, " The role of dynamics in enzyme activity," Annu. Rev. Biophys. Biomol. Struct. 32, 69-92 (2003). 10.1146/annurev.biophys.32.110601.142445
22. K. Nam, X. Prat-Resina, M. Garcia-Viloca, L. S. Devi-Kesavan, and J. Gao, " Dynamics of an enzymatic substitution reaction in haloalkane dehalogenase," J. Am. Chem. Soc. 126, 1369-1376 (2004). 10.1021/ja039093l
23. A. Warshel, Computer Modeling of Chemical Reactions in Enzymes and Solutions (John Wiley & Sons, New York, 1991).
24. I. F. Thorpe, " Barriers to hydride transfer in wild type and mutant dihydrofolate reductase from E. coli," J. Phys. Chem. B 107, 14042-14051 (2003). 10.1021/jp035734n
25. S. R. Billeter, S. P. Webb, P. K. Agarwal, T. Iordanov, and S. Hammes-Schiffer, " Hydride transfer in liver alcohol dehydrogenase: Quantum dynamics, kinetic isotope effects, and role of enzyme motion," J. Am. Chem. Soc. 123, 11262-11272 (2001). 10.1021/ja011384b
26. A. Warshel, " Dynamics of enzymatic reactions," Proc. Natl. Acad. Sci. U. S. A. 81, 444-448 (1984). 10.1073/pnas.81.2.444
27. A. Warshel and W. W. Parson, " Dynamics of biochemical and biophysical reactions: Insight from computer simulations," Q. Rev. Biophys. 34, 563-670 (2001). 10.1017/S0033583501003730
28. A. Warshel, F. Sussman, and J.-K. Hwang, " Evaluation of catalytic free energies in genetically modified proteins," J. Mol. Biol. 201, 139-159 (1988). 10.1016/0022-2836(88)90445-7
29. J. Villà and A. Warshel, " Energetics and dynamics of enzymatic reactions," J. Phys. Chem. B 105, 7887-7907 (2001). 10.1021/jp011048h
30. D. Kern and E. R. Zuiderweg, " The role of dynamics in allosteric regulation," Curr. Opin. Struct. Biol. 13, 748-757 (2003). 10.1016/j.sbi.2003.10.008
31. M. Wolf-Watz, V. Thai, K. Henzler-Wildman, G. Hadjipavlou, E. Z. Eisenmesser, and D. Kern, " Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair," Nat. Struct. Mol. Biol. 11, 945-949 (2004). 10.1038/nsmb821
32. D. Kern, E. Z. Eisenmesser, and M. Wolf-Watz, " Enzyme dynamics during catalysis measured my NMR spectroscopy," Methods Enzymol. 394, 507-524 (2005). 10.1016/s0076-6879(05)94021-4
33. E. Z. Eisenmesser, O. Millet, W. Labeikovsky, D. M. Korzhnev, M. Wolf-Watz, D. A. Bosco, J. J. Skalicky, and L. E. Kay, " Intrinsic dynamics of an enzyme underlies catalysis," Nature 438, 117-121 (2005). 10.1038/nature04105
34. K. Henzler-Wildman and D. Kern, " Dynamic personalities of proteins," Nature 450, 964-972 (2007). 10.1038/nature06522
35. K. A. Henzler-Wildman, M. Lei, V. Thai, S. J. Kerns, M. Karplus, and D. Kern, " A hierarchy of timescales in protein dynamics is linked to enzyme catalysis," Nature 450, 913-916 (2007). 10.1038/nature06407
36. K. A. Henzler-Wildman, V. Thai, M. Lei, M. Ott, M. Wolf-Watz, T. Fenn, E. Pozharski, M. A. Wilson, G. A. Petsko, M. Karplus, C. G. Hubner, and D. Kern, " Intrinsic motions along an enzymatic reaction trajectory," Nature 450, 838-844 (2007). 10.1038/nature06410
37. S. Kale, G. Ulas, J. Song, G. W. Brudvig, W. Furey, and F. Jordan, " Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex," Proc. Natl. Acad. Sci. U. S. A. 105, 1158-1163 (2008). 10.1073/pnas.0709328105
38. S. Saen-Oon, M. Ghanem, V. L. Schramm, and S. D. Schwart, " Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase," Biophys. J. 94, 4078-4088 (2008). 10.1529/biophysj.107.121913
39. L. R. Masterson, C. Cheng, T. Yu, M. Tonelli, A. Kornev, S. S. Taylos, and G. Veglia, " Dynamics connect substrate recognition to catalysis in protein kinase A," Nat. Chem. Biol. 6, 821-828 (2010). 10.1038/nchembio.452
40. G. Bhabha, J. Lee, D. C. Ekiert, J. Gam, I. A. Wilson, H. J. Dyson, S. J. Benkovic, and P. E. Wright, " A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis," Science 332, 234-238 (2011). 10.1126/science.1198542
41. J. P. Klinman and A. Kohen, " Hydrogen tunneling links protein dynamics to enzyme catalysis," Annu. Rev. Biochem. 82, 471-496 (2013). 10.1146/annurev-biochem-051710-133623
42. P. Singh, K. Francis, and A. Kohen, " Network of remote and local protein dynamics in dihydrofolate reductase catalysis," ACS Catal. 5, 3067-3073 (2015). 10.1021/acscatal.5b00331
43. J. Villali and D. Kern, " Choreographing an enzyme's dance," Curr. Opin. Chem. Biol. 14, 636-643 (2010). 10.1016/j.cbpa.2010.08.007
44. A. Warshel and Z. T. Chu, " Quantum corrections for rate constants of diabatic and adiabatic reactions in solutions," J. Chem. Phys. 93, 4003-4015 (1990). 10.1063/1.458785
45. J.-K. Hwang, Z. T. Chu, A. Yadav, and A. Warshel, " Simulations of quantum mechanical corrections for rate constants of hydride-transfer reactions in enzymes and solutions," J. Phys. Chem. 95, 8445-8448 (1991). 10.1021/j100175a009
46. S. C. Sharma and J. P. Klinman, " Experimental evidence for hydrogen tunneling when the isotopic Arrhenius prefactor (AH/AD) is unity," J. Am. Chem. Soc. 130, 17632-17633 (2008). 10.1021/ja806354w
47. A. Shurki and A. Warshel, " Structure/function correlations of proteins using MM, QM/MM, and related approaches: Methods, concepts, pitfalls, and current progress," Adv. Protein Chem. 66, 249-313 (2003). 10.1016/s0065-3233(03)66007-9
48. C. H. Bennett, " Molecular dynamics and transition state theory: The simulation of infrequent events," in Algorithms for Chemical Computations, edited by R. E. Christofferson (ACS, Washington, DC, 1977), pp. 63-97.
49. J. C. Keck, " Variational theory of reaction rates," Adv. Chem. Phys. 13, 85-121 (1966). 10.1002/9780470140154.ch5
50. E. K. Grimmelmann, J. C. Tully, and E. Helfand, " Molecular-dynamics of infrequent events-Thermal-desorption of xenon from a platinum surface," J. Chem. Phys. 74, 5300-5310 (1981). 10.1063/1.441696
51. A. Warshel and 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, 227-249 (1976). 10.1016/0022-2836(76)90311-9
52. D. Chandler, " Statistical-mechanics of isomerization dynamics in liquids and transition-state approximation," J. Chem. Phys. 68, 2959-2970 (1978). 10.1063/1.436049
53. R. O. Rosenberg, B. J. Berne, and D. Chandler, " Isomerization dynamics in liquids by molecular dynamics," Chem. Phys. Lett. 75, 162-168 (1980). 10.1016/0009-2614(80)80487-8
54. J. B. Anderson, " Predicting rare events in molecular dynamics," Adv. Chem. Phys. 91, 381-431 (1995). 10.1002/9780470141502.ch5
55. L. Y. P. Luk, J. J. Ruiz-Pernia, W. M. Dawson, M. Roca, E. J. Loveridge, D. R. Glowacki, J. N. Harvey, A. J. Mulholland, I. Tunon, V. Moliner, and R. K. Allemann, " Unraveling the role of protein dynamics in dihydrofolate reductase catalysis," Proc. Natl. Acad. Sci. U. S. A. 110, 16344-16349 (2013). 10.1073/pnas.1312437110
56. H. Liu and A. Warshel, " The catalytic effect of dihydrofolate reductase and its mutants is determined by reorganization energies," Biochemistry 46, 6011-6025 (2007). 10.1021/bi700201w
57. A. Warshel, " Molecular dynamics simulations of biological reactions," Acc. Chem. Res. 35, 385-395 (2002). 10.1021/ar010033z
58. D. D. Boehr, H. J. Dyson, and P. E. Wright, " An NMR perspective on enzyme dynamics," Chem. Rev. 106, 3055-3079 (2006). 10.1021/cr050312q
59. N2 reaction of dehalogenase as a general benchmark," J. Am. Chem. Soc. 126, 15167-15179 (2004). 10.1021/ja047151c
60. A. G. Palmer, C. D. Kroenke, and J. P. Loria, " Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules," Methods Enzymol. 339, 204-238 (2001). 10.1016/s0076-6879(01)39315-1
61. A. G. Palmer, " NMR characterization of the dynamics of biomacromolecules," Chem. Rev. 104, 3623-3640 (2004). 10.1021/cr030413t
62. M. Akke, " NMR methods for characterizing microsecond to millisecond dynamics in recognition and catalysis," Curr. Opin. Struct. Biol. 12, 642-647 (2002). 10.1016/S0959-440X(02)00369-X
63. T. I. Igumenova, K. K. Frederick, and J. A. Wand, " Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution," Chem. Rev. 106, 1672-1699 (2006). 10.1021/cr040422h
64. V. A. Jarymowycz and M. J. Stone, " Fast time scale dynamics of protein backbones: NMR relaxation methods, applications, and functional consequences," Chem. Rev. 106, 1624-1671 (2006). 10.1021/cr040421p
65. U. Brath, M. Akke, D. Yang, L. E. Kay, and F. A. A. Mulder, " Functional dynamics of human FKBP12 revealed by methyl 13C rotating frame relaxation dispersion NMR spectroscopy," J. Am. Chem. Soc. 128, 5718-5727 (2006). 10.1021/ja0570279
66. E. T. Oljeniczak, M.-M. Zhou, and S. W. Fesik, " Changes in the NMR-derived motional parameters of the insulin receptor substrate 1 phosphotyrosine binding domain upon binding of an interleukin 4 receptor phosphopeptide," Biochemistry 36, 4118-4124 (1997). 10.1021/bi963050i
67. A. L. Lee, S. A. Kinnear, and A. J. Wand, " Redistribution and loss of side chain entropy upon formation of a calmodulin-peptide complex," Nat. Struct. Biol. 7, 72-77 (2000). 10.1038/71280
68. J. J. Falke, " A moving story," Science 295, 1480-1481 (2002). 10.1126/science.1069823
69. G. H. Li and Q. Cui, " What is so special about Arg 55 in the catalysis of cyclophilin A? Insights from hybrid QM/MM simulations," J. Am. Chem. Soc. 125, 15028-15038 (2003). 10.1021/ja0367851
70. U. Doshi, L. C. McGowan, S. T. Ladani, and D. Hamelberg, " Resolving the complex role of enzyme conformational dynamics in catalytic function," Proc. Natl. Acad. Sci. U. S. A. 109, 5699-5704 (2012). 10.1073/pnas.1117060109
71. D. M. Epstein, S. J. Benkovic, and P. E. Wright, " Dynamics of the dihydrofolate reductase folate complex-Catalytic sites and regions known to undergo conformational change exhibit diverse dynamical features," Biochemistry 34, 11037-11048 (1995). 10.1021/bi00035a009
72. J. R. Schnell, H. J. Dyson, and P. E. Wright, " Structure, dynamics, and catalytic function of dihydrofolate reductase," Annu. Rev. Biophys. Biomol. Struct. 33, 119-140 (2004). 10.1146/annurev.biophys.33.110502.133613
73. A. J. Adamczyk, J. Cao, S. C. Kamerlin, and A. Warshel, " Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions," Proc. Natl. Acad. Sci. USA 108, 14115-14120 (2011). 10.1073/pnas.1111252108
74. E. J. Loveridge, E. M. Behiry, J. Guo, and R. K. Allemann, " Evidence that a 'dynamic knockout' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis," Nat. Chem. 292-297 (2012). 10.1038/nchem.1296
75. Y. Fan, A. Cembran, S. Ma, and J. Gao, " Connecting protein conformational dynamics with catalytic function as illustrated in dihydrofolate reductase," Biochemistry 52, 2036-2049 (2013). 10.1021/bi301559q
76. N. Boekelheide, R. Salomon-Ferrer, and T. F. Miller, " Dynamics and dissipation in enzyme catalysis," Proc. Natl. Acad. Sci. U. S. A. 108, 16159-16163 (2011). 10.1073/pnas.1106397108
77. M. Akke, " Out of hot water," Nat. Struct. Mol. Biol. 11, 912-913 (2004). 10.1038/nsmb1004-912
78. R. H. Austin, K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. Gunsalus, " Dynamics of ligand binding to myoglobin," Biochemistry 14, 5355-5373 (1979). 10.1021/bi00695a021
79. H. P. Lu, L. Xun, and X. S. Xie, " Single-molecule enzymatic dynamics," Science 282, 1877-1882 (1998). 10.1126/science.282.5395.1877
80. A. V. Pisliakov, J. Cao, S. C. Kamerlin, and A. Warshel, " Enzyme millisecond conformational dynamics do not catalyze the chemical step," Proc. Natl. Acad. Sci. U. S. A. 106, 17359-17364 (2009). 10.1073/pnas.0909150106
81. S. C. L. Kamerlin and A. Warshel, " Multiscale modeling of biological functions," Phys. Chem. Chem. Phys. 13, 10401-10411 (2011). 10.1039/c0cp02823a
82. B. R. Prasad, S. C. L. Kamerlin, J. Florián, and A. Warshel, " Prechemistry barriers and checkpoints do not contribute to fidelity and catalysis as long as they are not rate limiting," Theor. Chem. Acc. 131, 1288 (2012). 10.1007/s00214-012-1288-6
83. B. R. Prasad and A. Warshel, " Prechemistry versus preorganization in DNA replication fidelity," Proteins: Struct. Funct. Bioinf. 79, 2900-2919 (2011). 10.1002/prot.23128
84. S. Kirmizialtin, K. A. Johnson, and R. Elber, " Enzyme selectivity of HIV reverse transcriptase: Conformations, ligands and free energy partition," J. Phys. Chem. B 119, 11513-11526 (2015). 10.1021/acs.jpcb.5b05467
85. T. H. Rod, J. L. Radkiewicz, and C. L. Brooks, " Correlated motion and the effect of distal mutations in dihydrofolate reductase," Proc. Natl. Acad. Sci. U. S. A. 100, 6980-6985 (2003). 10.1073/pnas.1230801100
86. S. Hammes-Schiffer, " Quantum-classical simulation methods for hydrogen transfer in enzymes: A case study of dihydrofolate reductase," Curr. Opin. Struct. Biol. 14, 192-201 (2004). 10.1016/j.sbi.2004.03.008
87. J. B. Watney, P. K. Agarwal, and S. Hammes-Schiffer, " Effect of mutation on enzyme motion in dihydrofolate reductase," J. Am. Chem. Soc. 125, 3745-3750 (2003). 10.1021/ja028487u
88. M. I. Franco, L. Turin, A. Mershin, and E. M. C. Skoulakis, " Molecular vibration-sensing component in Drosophila melanogaster olfaction," Proc. Natl. Acad. Sci. U. S. A. 108, 3797-3802 (2011). 10.1073/pnas.1012293108
89. T. P. Hettinger, " Olfaction is a chemical sense, not a spectral sense," Proc. Natl. Acad. Sci. U. S. A. 108, E349 (2011). 10.1073/pnas.1103992108
90. A. Warshel and J. K. Hwang, " Simulation of the dynamics of electron transfer reactions in polar solvent: Semiclassical trajectories and dispersed polaron approaches," J. Chem. Phys. 84, 4938-4957 (1986). 10.1063/1.449981
91. D. Antoniou, S. Caratzoulas, C. Kalyanaraman, J. S. Mincer, and S. D. Schwartz, " Barrier passage and protein dynamics in enzymatically catalyzed reactions," Eur. J. Biochem. 269, 3103-3112 (2002). 10.1046/j.1432-1033.2002.03021.x
92. J. E. Basner and S. D. Schwartz, " Donor-acceptor distance and protein promoting vibration coupling to hydride transfer: A possible mechanism for kinetic control in isozymes of human lactate dehydrogenase," J. Phys. Chem. B 108, 444-451 (2004). 10.1021/jp0364349
93. S. Nunez, D. Antoniou, V. L. Schramm, and S. D. Schwartz, " Promoting vibrations in human purine nucleoside phosphorylase. A molecular dynamics and hybrid quantum mechanical/molecular mechanical study," J. Am. Chem. Soc. 126, 15720-15729 (2004). 10.1021/ja0457563
94. A. Warshel, " Dynamics of reactions in polar-solvents-Semi-classical trajectory studies of electron-transfer and proton-transfer reactions," J. Phys. Chem. 86, 2218-2224 (1982). 10.1021/j100209a016
95. M. J. Knapp, K. Rickert, and J. P. Klinman, " Temperature-dependent isotope effects in soybean lipoxygenase-1: Correlating hydrogen tunneling with protein dynamics," J. Am. Chem. Soc. 124, 3865-3874 (2002). 10.1021/ja012205t
96. S. Hay and N. S. Scrutton, "Good vibrations in enzyme-catalyzed reactions," Nat. Chem. 4 (3), 161-168 (2012). 10.1038/nchem.1223
97. S. C. L. Kamerlin, J. Mavri, and A. Warshel, " Examining the case for the effect of barrier compression on tunneling, vibrationally enhanced catalysis, catalytic entropy and related issues," FEBS Lett. 584, 2759-2766 (2010). 10.1016/j.febslet.2010.04.062
98. M. Roca, H. Liu, B. Messer, and A. Warshel, " On the relationship between thermal stability and catalytic power of enzymes," Biochemistry 46, 15076-15088 (2007). 10.1021/bi701732a
99. B. Peters, " Transition-state theory dynamics and narrow time scale separation in the rate-promoting vibration model of enzyme catalysis," J. Chem. Theory Comput. 6, 1447-1454 (2010). 10.1021/ct100051a
100. S. Hay, L. O. Johannissen, M. J. Sutcliffe, and N. S. Scrutton, " Barrier compression and its contribution to both classical and quantum mechanical aspects of enzyme catalysis," Biophys. J. 98, 121-128 (2010). 10.1016/j.bpj.2009.09.045
101. J. Y. Zhang and J. P. Klinman, " Enzymatic methyl transfer: Role of an active site residue in generating active site compaction that correlates with catalytic efficiency," J. Am. Chem. Soc. 133, 17134 (2011). 10.1021/ja207467d
102. J. Lameira, R. P. Bora, Z. T. Chu, and A. Warshel, " Methyltransferases do not work by compression, cratic, or desolvation effects, but by electrostatic preorganization," Proteins: Struct. Funct. Bioinf. 83, 318-330 (2015). 10.1002/prot.24717
103. M. Roca, S. Martí, J. Andrés, V. Moliner, I. Tuñón, J. Bertrán, and I. H. Williams, " Theoretical modeling of enzyme catalytic power: Analysis of "cratic" and electrostatic factors in catechol O-methyltransferase," J. Am. Chem. Soc. 125, 7726-7737 (2003). 10.1021/ja0299497
104. J. Zhang, H. J. Kulik, T. J. Martinez, and J. P. Klinman, " Mediation of donor-acceptor distance in an enzymatic methyl transfer reaction," Proc. Natl. Acad. Sci. U. S. A. 112, 7954-7959 (2015). 10.1073/pnas.1506792112
105. M. Štrajbl, A. Shurki, M. Kato, and A. Warshel, " Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization," J. Am. Chem. Soc. 125, 10228-10237 (2003). 10.1021/ja0356481
106. M. J. Knapp and J. P. Klinman, " Environmentally coupled hydrogen tunneling-Linking catalysis to dynamics," Eur. J. Biochem. 269, 3113-3121 (2002). 10.1046/j.1432-1033.2002.03022.x
107. X.-Z. Liang and J. P. Klinman, " Structural bases for hydrogen tunneling in enzymes: Progress and puzzles," Curr. Opin. Struct. Biol. 14, 648-655 (2004). 10.1016/j.sbi.2004.10.008
108. S. J. Benkovic, G. G. Hammes, and S. Hammes-Schiffer, " Free-energy landscape of enzyme catalysis," Biochemistry 47, 3317-3321 (2008). 10.1021/bi800049z
109. M. K. Prakash and R. A. Marcus, " An interpretation of fluctuations in enzyme catalysis rate, spectral diffusion, and radiative component of lifetimes in terms of electric field fluctuations," Proc. Natl. Acad. Sci. U. S. A. 104, 15982-15987 (2007). 10.1073/pnas.0707859104
110. C. A. Arnaud, " Enzymes' many movements," Chem. Eng. News 87, 34-36 (2009). 10.1021/cen-v087n017.p034
111. S. Kumar, B. Y. Ma, C. J. Tsai, N. Sinha, and R. Nussinov, " Folding and binding cascades: Dynamic landscapes and population shifts," Protein Sci. 9, 10-19 (2000). 10.1110/ps.9.1.10
112. W. Min, S. Xie, and B. Bagchi, " Two-dimensional reaction free energy surfaces of catalytic reaction: Effects of protein conformational dynamics on enzyme catalysis," J. Phys. Chem. B 112, 454-466 (2008). 10.1021/jp076533c
113. Y. Xiang, M. F. Goodman, W. A. Beard, S. H. Wilson, and A. Warshel, " Exploring the role of large conformational changes in the fidelity of DNA polymerase β," Proteins 70, 231-247 (2008). 10.1002/prot.21668
114. M. Roca, B. Messer, D. Hilvert, and A. Warshel, " On the relationship between folding and chemical landscapes in enzyme catalysis," Proc. Natl. Acad. Sci. U. S. A. 105, 13877-13882 (2008). 10.1073/pnas.0803405105
115. J. Florián, M. F. Goodman, and A. Warshel, " Computer simulations of protein functions: Searching for the molecular origin of the replication fidelity of DNA polymerases," Proc. Natl. Acad. Sci. U. S. A. 102, 6819-6824 (2005). 10.1073/pnas.0408173102
116. K. Vamvaca, B. Vögeli, P. Kast, K. Pervushin, and D. Hilvert, " An enzymatic molten globule: Efficient coupling of folding and catalysis," Proc. Natl. Acad. Sci. U. S. A. 101, 12860-12864 (2004). 10.1073/pnas.0404109101
117. K. Pervushin, K. Vamvaca, B. Vögeli, and D. Hilvert, " Structure and dynamics of a molten globular enzyme," Nat. Struct. Mol. Biol. 14, 1202-1206 (2007). 10.1038/nsmb1325
118. Z. Nagel and J. P. Klinman, " Tunneling and dynamics in enzymatic hydride transfer," Chem. Rev. 106, 3095-3118 (2006). 10.1021/cr050301x
119. J. P. Klinman, " An integrated model for enzyme catalysis emerges from studies of hydrogen tunneling," Chem. Phys. Lett. 471, 179-193 (2009). 10.1016/j.cplett.2009.01.038
120. J. Villà, M. Štrajbl, T. M. Glennon, Y. Y. Sham, Z. T. Chu, and A. Warshel, " How important are entropy contributions in enzymatic catalysis?," Proc. Natl. Acad. Sci. U. S. A. 97, 11899-11904 (2000). 10.1073/pnas.97.22.11899
121. P. Schopf, M. J. L. Mills, and A. Warshel, " The entropic contributions in vitamin B-12 enzymes still reflect the electrostatic paradigm," Proc. Natl. Acad. Sci. U. S. A. 112, 4328-4333 (2015). 10.1073/pnas.1503828112
122. D. Ringe and G. A. Petsko, " Quantum enzymology-Tunnel vision," Nature 399, 417-418 (1999). 10.1038/20819
123. A. Kohen and J. P. Klinman, " Protein flexibility correlates with degree of hydrogen tunneling in thermophilic and mesophilic alcohol dehydrogenases," J. Am. Chem. Soc. 122, 10738-10739 (2000). 10.1021/ja002229k
124. G. P. Miller and S. J. Benkovic, " Stretching excercises-Flexibility in dihydrofolate reductase catalysis," Chem. Biol. 5, R105-R113 (1998). 10.1016/S1074-5521(98)90616-0
125. P. T. Rajagopalan and S. J. Benkovic, " Preorganization and protein dynamics in enzyme catalysis," Chem. Rec. 2, 24-36 (2002). 10.1002/tcr.10009
126. G. G. Dodson, D. P. Lane, and C. S. Verma, " Molecular simulations of protein dynamics: New windows on mechanisms in biology," EMBO Rep. 9, 144-150 (2008). 10.1038/sj.embor.7401160
127. G. Maglia, M. H. Javed, and R. K. Allemann, " Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga maritima," Biochem. J. 374, 529-535 (2003). 10.1042/bj20030412
128. A. Wrba, A. Schwieger, V. Schultes, R. Jaenicke, and P. Zavodsky, " Extremely thermostable D-glyceraldehyde-3-phosphate dehydrogenase from the eubacterium Thermotoga maritima," Biochemistry 29, 7584-7592 (1990). 10.1021/bi00485a007
129. M. Ben-David, J. L. Sussman, C. I. Maxwell, K. Szeler, S. C. L. Kamerlin, and D. S. Tawfik, " Catalytic stimulation by restrained active-site floppiness-The case of high density lipoprotein-bound serum paraoxonase-1," J. Mol. Biol. 427, 1359-1374 (2015). 10.1016/j.jmb.2015.01.013
130. G. V. Isaksen, J. Aqvist, and B. O. Brandsdal, " Protein surface softness is the origin of enzyme cold-adaptation of trypsin," PLoS Comp. Biol. 10, e1003813 (2014). 10.1371/journal.pcbi.1003813
131. P. F. Cook, Enzyme Mechanism from Isotope Effects (CRC Press, Boca Raton, Florida, 1991).
132. A. Kohen and H. Limbarch, Isotopic Effects in Chemistry and Biology (Taylor & Francis Group, LLC, Boca Raton, 2006).
133. J. P. Klinman, " Linking protein structure and dynamics to catalysis: The role of hydrogen tunneling," Philos. Trans. R. Soc., B. 361, 1323-1331 (2006). 10.1098/rstb.2006.1870
134. S.-C. Tsai and J. P. Klinman, " Probes of hydrogen tunneling with horse liver alcohol dehydrogenase at subzero temperature," Biochemistry 40, 2303-2311 (2001). 10.1021/bi002075l
135. B. J. Bahnson, T. D. Colby, J. K. Chin, B. M. Goldstein, and J. P. Klinman, " A link between protein structure and enzyme catalyzed hydrogen tunneling," Proc. Natl. Acad. Sci. U. S. A. 94, 12797-12802 (1997). 10.1073/pnas.94.24.12797
136. K. L. Grant and J. P. Klinman, " Evidence that both protium and deuterium undergo significant tunneling in the reaction catalyzed by bovine serum amine oxidase," Biochemistry 28, 6597-6605 (1989). 10.1021/bi00442a010
137. T. Jonsson, M. H. Glickman, S. J. Sun, and J. P. Klinman, " Experimental evidence for extensive tunneling of hydrogen in the lipoxygenase reaction: Implications for enzyme catalysis," J. Am. Chem. Soc. 118, 10319-10320 (1996). 10.1021/ja961827p
138. A. Kohen, T. Jonsson, and J. P. Klinman, " Effects of protein glycosylation on catalysis: Changes in hydrogen tunneling and enthalpy of activation in the glucose oxidase reaction," Biochemistry 36, 6854 (1997). 10.1021/bi975003b
139. S. Hay and N. S. Scrutton, " Good vibrations in enzyme-catalysed reactions," Nat Chem 4, 161-168 (2012). 10.1038/nchem.1223
140. P. Ball, " Enzymes: By chance, or by design?," Nature 431, 396-397 (2004). 10.1038/431396a
141. J. K. Hwang and A. Warshel, " How important are quantum mechanical nuclear motions in enzyme catalysis?," J. Am. Chem. Soc. 118, 11745-11751 (1996). 10.1021/ja962007f
142. M. H. M. Olsson, J. Mavri, and A. Warshel, " 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., B 361, 1417-1432 (2006). 10.1098/rstb.2006.1880
143. H. Liu and A. Warshel, " Origin of the temperature dependence of isotope effects in enzymatic reactions: The case of dihydrofolate reductase," J. Phys. Chem. B 111, 7852-7861 (2007). 10.1021/jp070938f
144. D. T. Major, A. Heroux, A. M. Orville, M. P. Valley, P. F. Fitzpatrick, and J. L. Gao, " Differential quantum tunneling contributions in nitroalkane oxidase catalyzed and the uncatalyzed proton transfer reaction," Proc. Natl. Acad. Sci. U. S. A. 106, 20734-20739 (2009). 10.1073/pnas.0911416106
145. 2OH on the distance between reactants when catalyzed by horse liver alcohol dehydrogenase and 203 single point mutants," Bioorg. Chem. 27, 289-296 (1999). 10.1006/bioo.1999.1139
146. J. P. Klinman, " Quantum mechanical effects in enzyme-catalysed hydrogen transfer reactions," Trends Biochem. Sci. 14, 368-373 (1989). 10.1016/0968-0004(89)90010-8
147. J. S. Mincer and S. D. Schwartz, " A computational method to identify residues important in creating a protein promoting vibration in enzymes," J. Phys. Chem. B 107, 366-371 (2003). 10.1021/jp027017j
148. M. J. Sutcliffe and N. S. Scrutton, " Enzymology takes a quantum leap forward," Philos. Trans. R. Soc., A 358, 367-386 (2000). 10.1098/rsta.2000.0536
149. E. Hatcher, A. V. Soudackov, and S. Hammes-Schiffer, " Proton-coupled electron transfer in soybean lipoxygenase: Dynamical behavior and temperature dependence of kinetic isotope effects," J. Am. Chem. Soc. 129, 187-196 (2007). 10.1021/ja0667211
150. S. C. L. Kamerlin and A. Warshel, " An analysis of all the relevant facts and arguments indicates that enzyme catalysis does not involve large contributions from nuclear tunneling," J. Phys. Org. Chem. 23, 677-684 (2009). 10.1002/poc.1620
151. A. M. Kuznetsov and J. Ulstrop, " Proton and hydrogen atom tunnelling in hydrolytic and redox enzyme catalysis," Can. J. Chem. 77, 1085-1096 (1999). 10.1139/cjc-77-5-6-1085
152. L. Wang, N. M. Goodey, S. J. Benkovic, and A. Kohen, " Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase," Proc. Natl. Acad. Sci. U. S. A 103, 15753-15758 (2006). 10.1073/pnas.0606976103
153. W. J. Bruno and W. Bialek, " Vibrationally enhanced tunneling as a mechanism for enzymatic hydrogen transfer," Biophys. J. 63, 689-699 (1992). 10.1016/S0006-3495(92)81654-5
154. B. M. Dunn and T. C. Bruice, " Physical organic models for the mechanism of lysozyme action," Adv. Enzymol. Relat. Areas Mol. Biol. 37, 1-60 (2006). 10.1002/9780470122822.ch1
155. T. H. Fife, S. H. Jaffe, and R. Natarajan, " Intramolecular general acid and electrostatic catalysis in acetal hydrolysis. Hydrolysis of 2-(substituted phenoxy)-6-carboxytetrahydropyrans and 2-alkoxy-6-carboxytetrahydropyrans," J. Am. Chem. Soc. 113, 7646-7653 (1991). 10.1021/ja00020a028
156. W. P. Jencks, " Binding energy, specificity, and enzymic catalysis: The circe effect," in Advances in Enzymology and Related Areas of Molecular Biology, edited by A. Meister (J. Wiley & Sons, Inc., New York, 1975), Vol. 43, pp. 219-410.
157. A. Barrozo, F. Duarte, P. Bauer, A. T. P. Carvalho, and S. C. L. Kamerlin, " Cooperative electrostatic interactions drive functional evolution in the alkaline phosphatase superfamily," J. Am. Chem. Soc. 137, 9061-9076 (2015). 10.1021/jacs.5b03945
158. Z. D. Nagel and J. P. Klinman, " A 21st century revisionist's view at a turning point in enzymology," Nat. Chem. Biol. 5, 543-550 (2009). 10.1038/nchembio.204
159. S. D. Fried, S. Bagchi, and S. G. Boxer, " Extreme electric fields power catalysis in the active site of ketosteroid isomerase," Science 346, 1510-1514 (2014). 10.1126/science.1259802
160. A. Warshel, " Multiscale modeling of biological functions: From enzymes to molecular machines (Nobel Lecture)," Angw. Chem. Int. Ed. 53, 10020-10031 (2014). 10.1002/anie.201403689
161. a, redox reactions, and solvation free energies," J. Phys. Chem. B 113, 1253-1272 (2009). 10.1021/jp8071712
162. E. Rosta, M. Klähn, and A. Warshel, " Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions," J. Phys. Chem. B 110, 2934-2941 (2006). 10.1021/jp057109j
163. M. Štrajbl, G. Hong, and A. Warshel, " Ab initio QM/MM simulation with proper sampling: 'First principle' calculations of the free energy of the autodissociation of water in aqueous solution," J. Phys. Chem. B 106, 13333-13343 (2002). 10.1021/jp021625h
164. N. V. Plotnikov and A. Warshel, " Exploring, refining, and validating the paradynamics QM/MM sampling," J. Phys. Chem. B 116, 10342-10356 (2012). 10.1021/jp304678d
165. S. C. L. Kamerlin and A. Warshel, " The EVB as a quantitative tool for formulating simulations and analyzing biological and chemical reactions," Faraday Discuss. 145, 71-106 (2010). 10.1039/B907354J
166. R. A. Kuharski, J. S. Bader, D. Chandler, M. Sprik, M. L. Klein, and R. W. Impey, " Molecular model for aqueous Ferrous-Ferric electron transfer," J. Chem. Phys. 89, 3248-3257 (1988). 10.1063/1.454929
167. M. Cascella, A. Magistrato, I. Tavernelli, P. Carloni, and U. Rothlisberger, " Role of protein frame and solvent for the redox properties of azurin from Pseudonomas aeruginosa," Proc. Natl. Acad. Sci. U. S. A. 103, 19641-19646 (2006). 10.1073/pnas.0607890103
168. J. Blumberger, L. Bernasconi, I. Tavernelli, R. Vuilleumier, and M. Sprik, " Electronic structure and solvation of copper and silver ions: A theoretical picture of a model aqueous redox reaction," J. Am. Chem. Soc. 126, 3928-3938 (2004). 10.1021/ja0390754
169. Y. Kim, J. C. Corchado, J. Villà, J. Xing, and D. G. Truhlar, " Multiconfiguration molecular mechanics algorithm for potential energy surfaces of chemical reactions," J. Chem. Phys. 112, 2718-2735 (2000). 10.1063/1.480846
170. J. Florián, " Comment on molecular mechanics for chemical reactions," J. Phys. Chem. A 106, 5046-5047 (2002). 10.1021/jp0135510
171. M. Higashi and D. G. Truhlar, " Electrostatically embedded multiconfiguration molecular mechanics based on the combined density functional and molecular mechanical method," J. Chem. Theor. Comput. 4, 790-803 (2008). 10.1021/ct800004y
172. M. P. Frushicheva, J. Cao, Z. T. Chu, and A. Warshel, " Exploring challenges in rational enzyme design by simulating the catalysis in artificial Kemp eliminase," Proc. Natl. Acad. Sci. U. S. A. 107, 16869-16874 (2010). 10.1073/pnas.1010381107
173. M. P. Frushicheva, J. Cao, and A. Warshel, " Challenges and advances in validating enzyme design proposals: The case of Kemp eliminase catalysis," Biochemistry 50, 3849-3858 (2011). 10.1021/bi200063a
174. M. P. Frushicheva, M. J. L. Mills, P. Schopf, M. K. Singh, R. B. Prasad, and A. Warshel, " Computer aided enzyme design and catalytic concepts," Curr. Opin. Chem. Biol. 21, 56-62 (2014). 10.1016/j.cbpa.2014.03.022
175. S. Hammes-Schiffer and S. J. Benkovic, " Relating protein motion to catalysis," Annu. Rev. Biochem. 75, 519-541 (2006). 10.1146/annurev.biochem.75.103004.142800
176. S. C. L. Kamerlin and A. Warshel, " Reply to Karplus: Conformational dynamics have no role in the chemical step," Proc. Natl. Acad. Sci. U. S. A. 107, E72 (2010). 10.1073/pnas.1002658107
177. A. Kohen, " Role of dynamics in enzyme catalysis: Substantial versus semantic controversies," Acc. Chem. Res. 48, 466-473 (2015). 10.1021/ar500322s
178. J. K. Lassila, " Conformational diversity and computational enzyme design," Curr. Opin. Chem. Biol. 14, 676-682 (2010). 10.1016/j.cbpa.2010.08.010
179. S. M. C. Gobeil, C. M. Clouthier, J. Park, D. Gagne, A. M. Berghuis, N. Doucet, and J. N. Pelletier, " Maintenance of native-like protein dynamics may not be required for engineering functional proteins," Chem. Biol. 21, 1330-1340 (2014). 10.1016/j.chembiol.2014.07.016
180. N. Tokuriki and C. J. Jackson, " Enzyme dynamics and engineering: One step at a time," Chem. Biol. 21, 1259-1260 (2014). 10.1016/j.chembiol.2014.10.003
181. A. Bar-Even, R. Milo, E. Noor, and D. S. Tawfik, " The moderately efficient enzyme: Futile encounters and enzyme floppiness," Biochemistry 54, 4969-4977 (2015). 10.1021/acs.biochem.5b00621
182. N2 enzyme reaction using free-energy surfaces and solvent coordinates," Nat. Chem. 5, 566-571 (2013). 10.1038/nchem.1660
183. D. R. Glowacki, J. N. Harvey, and A. J. Mulholland, " Taking Ockham's razor to enzyme dynamics and catalysis," Nature Chem. 4, 169-176 (2012). 10.1038/nchem.1244
184. I. Tunon, D. Laage, and J. T. Hynes, " Are there dynamical effects in enzyme catalysis? Some thoughts concerning the enzymatic chemical step," Arch. Biochem. Biophys. 582, 42-55 (2015). 10.1016/j.abb.2015.06.004