The Quest for Accurate Theoretical Models of Metalloenzymes …
457
3. Siegbahn PE, Blomberg MR (2010) Quantum chemical studies of proton-coupled electron
transfer in metalloenzymes. Chem Rev 110:7040–7061. https://doi.org/10.1021/cr100070p
4. Valdez CE, Smith QA, Nechay MR, Alexandrova AN (2014) Mysteries of metals in metalloenzymes. Acc Chem Res 47:3110–3117. https://doi.org/10.1021/ar500227u
5. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. Chem
Phys 98:5648–5652
6. Meunier B, De Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by
cytochrome P450 enzymes. Chem Rev 104:3947–3980
7. Li D, Wang Y, Han K (2012) Recent density functional theory model calculations of drug
metabolism by cytochrome P450. Coord Chem Rev 256:1137–1150
8. Blomberg MRA, Borowski T, Himo F et al (2014) Quantum chemical studies of mechanisms
for metalloenzymes. Chem Rev 114:3601–3658. https://doi.org/10.1021/cr400388t
9. de Visser SP, Quesne MG, Martin B et al (2014) Computational modelling of oxygenation
processes in enzymes and biomimetic model complexes. Chem Commun 50:262–282. https://
doi.org/10.1039/c3cc47148a
10. Siegbahn EM, Crabtree RH (1997) Mechanism of C−H activation by diiron methane
monooxygenases: quantum chemical studies. J Am Chem Soc 119:3103–3113. https://doi.
org/10.1021/JA963939M
11. Timmins A, Saint-André M, de Visser SP (2017) Understanding how Prolyl-4-hydroxylase
structure steers a Ferryl Oxidant toward scission of a strong C-H Bond. J Am Chem Soc
139:9855–9866. https://doi.org/10.1021/jacs.7b02839
12. Timmins A, de Visser SP (2017) How are substrate binding and catalysis affected by mutating
Glu127 and Arg161 in Prolyl-4-hydroxylase? A QM/MM and MD study. Front Chem 5:94.
https://doi.org/10.3389/fchem.2017.00094
13. Gao J, Truhlar DG (2002) Quantum mechanical methods for enzyme kinetics. Annu Rev Phys
Chem 53:467–505
14. Senn HM, Thiel W (2007) QM/MM studies of enzymes. Curr Opin Chem Biol 11:182–187
15. Senn HM, Thiel W (2009) QM/MM methods for biomolecular systems. Angew Chemie Int
Ed 48:1198–1229. https://doi.org/10.1002/anie.200802019
16. van der Kamp MW, Mulholland AJ (2013) Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry 52:2708–2728
17. Warshel A, Levitt M (1976) 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. DOI: https://doi.org/0022-2836(76)90311-9 [pii]
18. Field MJ, Bash PA, Karplus M (1990) A combined quantum mechanical and molecular
mechanical potential for molecular dynamics simulations. J Comput Chem 11:700–733.
https://doi.org/10.1002/jcc.540110605
19. Rothlisberger U, Carloni P, Doclo K, Parrinello M (2000) A comparative study of galactose
oxidase and active site analogs based on QM/MM Car-Parrinello simulations. J Biol Inorg
Chem 5:236–250. https://doi.org/10.1007/s007750050368
20. Borowski T, Quesne M, Szaleniec M (2015) QM and QM/MM methods compared: Case
studies on reaction mechanisms of metalloenzymes. In: Advances in protein chemistry and
structural biology. Academic Press Inc, pp 187–224
21. Quesne MG, Borowski T, De Visser SP (2016) Quantum mechanics/molecular mechanics
modeling of enzymatic processes: caveats and breakthroughs. Chem—A Eur J 22:2562–2581.
https://doi.org/10.1002/chem.201503802
22. Mulholland AJ, Grant GH, Richards WG (1993) Computer modeling of enzyme catalyzed
reaction-mechanisms. Protein Eng 6:133–147
23. Siegbahn PEM (2001) Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes. J Comput Chem 22:1634–1645. https://doi.org/10.1002/jcc.1119
24. Sevastik R, Himo F (2007) Quantum chemical modeling of enzymatic reactions: the case of
4-oxalocrotonate tautomerase. Bioorg Chem 35:444–457
25. Georgieva P, Himo F (2010) Quantum chemical modeling of enzymatic reactions: the case of
histone lysine methyltransferase. J Comput Chem 31:1707–1714
457
3. Siegbahn PE, Blomberg MR (2010) Quantum chemical studies of proton-coupled electron
transfer in metalloenzymes. Chem Rev 110:7040–7061. https://doi.org/10.1021/cr100070p
4. Valdez CE, Smith QA, Nechay MR, Alexandrova AN (2014) Mysteries of metals in metalloenzymes. Acc Chem Res 47:3110–3117. https://doi.org/10.1021/ar500227u
5. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. Chem
Phys 98:5648–5652
6. Meunier B, De Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by
cytochrome P450 enzymes. Chem Rev 104:3947–3980
7. Li D, Wang Y, Han K (2012) Recent density functional theory model calculations of drug
metabolism by cytochrome P450. Coord Chem Rev 256:1137–1150
8. Blomberg MRA, Borowski T, Himo F et al (2014) Quantum chemical studies of mechanisms
for metalloenzymes. Chem Rev 114:3601–3658. https://doi.org/10.1021/cr400388t
9. de Visser SP, Quesne MG, Martin B et al (2014) Computational modelling of oxygenation
processes in enzymes and biomimetic model complexes. Chem Commun 50:262–282. https://
doi.org/10.1039/c3cc47148a
10. Siegbahn EM, Crabtree RH (1997) Mechanism of C−H activation by diiron methane
monooxygenases: quantum chemical studies. J Am Chem Soc 119:3103–3113. https://doi.
org/10.1021/JA963939M
11. Timmins A, Saint-André M, de Visser SP (2017) Understanding how Prolyl-4-hydroxylase
structure steers a Ferryl Oxidant toward scission of a strong C-H Bond. J Am Chem Soc
139:9855–9866. https://doi.org/10.1021/jacs.7b02839
12. Timmins A, de Visser SP (2017) How are substrate binding and catalysis affected by mutating
Glu127 and Arg161 in Prolyl-4-hydroxylase? A QM/MM and MD study. Front Chem 5:94.
https://doi.org/10.3389/fchem.2017.00094
13. Gao J, Truhlar DG (2002) Quantum mechanical methods for enzyme kinetics. Annu Rev Phys
Chem 53:467–505
14. Senn HM, Thiel W (2007) QM/MM studies of enzymes. Curr Opin Chem Biol 11:182–187
15. Senn HM, Thiel W (2009) QM/MM methods for biomolecular systems. Angew Chemie Int
Ed 48:1198–1229. https://doi.org/10.1002/anie.200802019
16. van der Kamp MW, Mulholland AJ (2013) Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry 52:2708–2728
17. Warshel A, Levitt M (1976) 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. DOI: https://doi.org/0022-2836(76)90311-9 [pii]
18. Field MJ, Bash PA, Karplus M (1990) A combined quantum mechanical and molecular
mechanical potential for molecular dynamics simulations. J Comput Chem 11:700–733.
https://doi.org/10.1002/jcc.540110605
19. Rothlisberger U, Carloni P, Doclo K, Parrinello M (2000) A comparative study of galactose
oxidase and active site analogs based on QM/MM Car-Parrinello simulations. J Biol Inorg
Chem 5:236–250. https://doi.org/10.1007/s007750050368
20. Borowski T, Quesne M, Szaleniec M (2015) QM and QM/MM methods compared: Case
studies on reaction mechanisms of metalloenzymes. In: Advances in protein chemistry and
structural biology. Academic Press Inc, pp 187–224
21. Quesne MG, Borowski T, De Visser SP (2016) Quantum mechanics/molecular mechanics
modeling of enzymatic processes: caveats and breakthroughs. Chem—A Eur J 22:2562–2581.
https://doi.org/10.1002/chem.201503802
22. Mulholland AJ, Grant GH, Richards WG (1993) Computer modeling of enzyme catalyzed
reaction-mechanisms. Protein Eng 6:133–147
23. Siegbahn PEM (2001) Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes. J Comput Chem 22:1634–1645. https://doi.org/10.1002/jcc.1119
24. Sevastik R, Himo F (2007) Quantum chemical modeling of enzymatic reactions: the case of
4-oxalocrotonate tautomerase. Bioorg Chem 35:444–457
25. Georgieva P, Himo F (2010) Quantum chemical modeling of enzymatic reactions: the case of
histone lysine methyltransferase. J Comput Chem 31:1707–1714