Mechanistic insight on the inhibition of D, D-carboxypeptidase from Mycobacterium tuberculosis by β-lactam antibiotics: an ONIOM acylation study. - 2022
[en] Mycobacterium tuberculosis cell wall is intricate and impermeable to many agents. A D, D-carboxypeptidase (DacB1) is one of the enzymes involved in the biosynthesis of cell wall peptidoglycan and catalyzes the terminal D-alanine cleavage from pentapeptide precursors. Catalytic activity and mechanism by which DacB1 functions is poorly understood. Herein, we investigated the acylation mechanism of DacB1 by β-lactams using a 6-membered ring transition state model that involves a catalytic water molecule in the reaction pathway. The full transition states (TS) optimization plus frequency were achieved using the ONIOM (B3LYP/6-31 + G(d): AMBER) method. Subsequently, the activation free energies were computed via single-point calculations on fully optimized structures using B3LYP/6-311++(d,p): AMBER and M06-2X/6-311++(d,p): AMBER with an electronic embedding scheme. The 6-membered ring transition state is an effective model to examine the inactivation of DacB1 via acylation by β-lactams antibiotics (imipenem, meropenem, and faropenem) in the presence of the catalytic water. The ΔG# values obtained suggest that the nucleophilic attack on the carbonyl carbon is the rate-limiting step with 13.62, 19.60 and 30.29 kcal mol-1 for Imi-DacB1, Mero-DacB1 and Faro-DacB1, respectively. The electrostatic potential (ESP) and natural bond orbital (NBO) analysis provided significant electronic details of the electron-rich region and charge delocalization, respectively, based on the concerted 6-membered ring transition state. The stabilization energies of charge transfer within the catalytic reaction pathway concurred with the obtained activation free energies. The outcomes of this study provide important molecular insight into the inactivation of D, D-carboxypeptidase by β-lactams.Communicated by Ramaswamy H. Sarma.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ntombela, Thandokuhle ; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Seupersad, Anya; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Maseko, Sibusiso Bonginkhost ; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Ibeji, Collins U; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Tolufashe, Gideon; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Maphumulo, Siyabonga Innocent; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Naicker, Tricia ; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Baijnath, Sooraj ; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Maguire, Glenn E M; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa ; School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
Govender, Thavendran ; Faculty of Science and Agriculture, Department of Chemistry, University of Zululand, Richards Bay, South Africa
Lamichhane, Gyanu; Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Honarparvar, Bahareh; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Kruger, Hendrik G ; Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
We thank the College of Health Sciences (CHS), MRC, and NRF for financial support. We are also grateful to the CHPC ( http://www.chpc.ac.za ) and UKZN cluster for computational resources. G Lamichhane was supported by award 1R21AI137720 from the National Institutes of Health (NIH), USA.
Bauschlicher, C. W., Jr. (1995). A comparison of the accuracy of different functionals. Chemical Physics Letters, 246 (1-2), 40–44. https://doi.org/10.1016/0009-2614(95)01089-R
Bayly, C. I., Cieplak, P., Cornell, W., & Kollman, P. A. (1993). A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. The Journal of Physical Chemistry, 97 (40), 10269–10280. https://doi.org/10.1021/j100142a004
Biovia, D. S. (2017). Discovery studio modeling environment. Release.
Boonsri, P., Kuno, M., & Hannongbua, S. (2011). Key interactions of the mutant HIV-1 reverse transcriptase/efavirenz: An evidence obtained from ONIOM method. MedChemComm, 2 (12), 1181–1187. https://doi.org/10.1039/c1md00162k
Calixto, A. R., Brás, N. F., Fernandes, P. A., & Ramos, M. J. (2014). Reaction mechanism of human renin studied by quantum mechanics/molecular mechanics (QM/MM) calculations. ACS Catalysis, 4 (11), 3869–3876. https://doi.org/10.1021/cs500497f
Case, D. A., Darden, T., Cheatham, T., Simmerling, C. L., Wang, J., Duke, R. E., Luo, R., Crowley, M., Walker, R. C., & Zhang, W. (2008). Amber 10. University of California.
Cordillot, M., Dubée, V., Triboulet, S., Dubost, L., Marie, A., Hugonnet, J.-E., Arthur, M., & Mainardi, J.-L. (2013). In vitro cross-linking of peptidoglycan by Mycobacterium tuberculosis L, D-transpeptidases and inactivation of these enzymes by carbapenems. Antimicrobial Agents and Chemotherapy, 57 (12), 5940–5945. https://doi.org/10.1128/AAC.01663-13
Correale, S., Ruggiero, A., Capparelli, R., Pedone, E., & Berisio, R. (2013). Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis. Acta Crystallographica. Section D, Biological Crystallography, 69 (Pt 9), 1697–1706. https://doi.org/10.1107/S0907444913013085
Dasgupta, A., Datta, P., Kundu, M., & Basu, J. (2006). The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division. Microbiology, 152 (Pt 2), 493–504. https://doi.org/10.1099/mic.0.28630-0
Demain, A. L., & Elander, R. P. (1999). The beta-lactam antibiotics: Past, present, and future. Antonie Van Leeuwenhoek, 75 (1-2), 5–19. https://doi.org/10.1023/A:1001738823146
Dennington, R., Keith, T., & Millam, J. (2009). GaussView, version 5. Semichem Inc.
Dhar, N., Dubée, V., Ballell, L., Cuinet, G., Hugonnet, J.-E., Signorino-Gelo, F., Barros, D., Arthur, M., & McKinney, J. D. (2015). Rapid cytolysis of Mycobacterium tuberculosis by faropenem, an orally bioavailable β-lactam antibiotic. Antimicrobial Agents and Chemotherapy, 59 (2), 1308–1319. https://doi.org/10.1128/AAC.03461-14
Dubée, V., Arthur, M., Fief, H., Triboulet, S., Mainardi, J.-L., Gutmann, L., Sollogoub, M., Rice, L. B., Ethève-Quelquejeu, M., & Hugonnet, J.-E. (2012). Kinetic analysis of Enterococcus faecium L, D-transpeptidase inactivation by carbapenems. Antimicrobial Agents and Chemotherapy, 56 (6), 3409–3411. https://doi.org/10.1128/AAC.06398-11
Erdemli, S. B., Gupta, R., Bishai, W. R., Lamichhane, G., Amzel, L. M., & Bianchet, M. A. (2012). Targeting the cell wall of Mycobacterium tuberculosis: Structure and mechanism of L,D-transpeptidase 2. Structure, 20 (12), 2103–2115. https://doi.org/10.1016/j.str.2012.09.016
Fakhar, Z., Govender, T., Lamichhane, G., Maguire, G. E., Kruger, H. G., & Honarparvar, B. (2017). Computational model for the acylation step of the β-lactam ring: Potential application for l, d-transpeptidase 2 in Mycobacterium tuberculosis. Journal of Molecular Structure, 1128, 94–102. https://doi.org/10.1016/j.molstruc.2016.08.049
Fakhar, Z., Naiker, S., Alves, C. N., Govender, T., Maguire, G. E., Lameira, J., Lamichhane, G., Kruger, H. G., & Honarparvar, B. (2016). A comparative modeling and molecular docking study on Mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis. Journal of Biomolecular Structure & Dynamics, 34 (11), 2399–2417. https://doi.org/10.1080/07391102.2015.1117397
Frisch, M., Trucks, G., Schlegel, H. B., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Mennucci, B., & Petersson, G. (2009). Gaussian 09, revision a. 02 (Vol. 200, p. 28). Gaussian Inc.
Gasteiger, J., & Marsili, M. (1980). Iterative partial equalization of orbital electronegativity–A rapid access to atomic charges. Tetrahedron, 36 (22), 3219–3228. https://doi.org/10.1016/0040-4020(80)80168-2
Gonzalez, C., & Schlegel, H. B. (1989). An improved algorithm for reaction path following. The Journal of Chemical Physics, 90 (4), 2154–2161. https://doi.org/10.1063/1.456010
Gupta, R., Lavollay, M., Mainardi, J.-L., Arthur, M., Bishai, W. R., & Lamichhane, G. (2010). The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. Nature Medicine, 16 (4), 466–469. https://doi.org/10.1038/nm.2120
Harvey, M., & De Fabritiis, G. (2009). An implementation of the smooth particle mesh Ewald method on GPU hardware. Journal of Chemical Theory and Computation, 5 (9), 2371–2377. https://doi.org/10.1021/ct900275y
Hornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., & Simmerling, C. (2006). Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins, 65 (3), 712–725. https://doi.org/10.1002/prot.21123
Ibeji, C. U., Tolufashe, G. F., Ntombela, T., Govender, T., Maguire, G. E., Lamichhane, G., Kruger, H. G., & Honarparvar, B. (2018). The catalytic role of water in the binding site of l,d-transpeptidase 2 within acylation mechanism: A QM/MM (ONIOM) modelling. Tuberculosis, 113, 222–230. https://doi.org/10.1016/j.tube.2018.10.005
Janin, Y. L. (2007). Antituberculosis drugs: Ten years of research. Bioorganic & Medicinal Chemistry, 15 (7), 2479–2513. https://doi.org/10.1016/j.bmc.2007.01.030
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79 (2), 926–935. https://doi.org/10.1063/1.445869
Kim, H. S., Kim, J., Im, H. N., Yoon, J. Y., An, D. R., Yoon, H. J., Kim, J. Y., Min, H. K., Kim, S.-J., Lee, J. Y., Han, B. W., & Suh, S. W. (2013). Structural basis for the inhibition of Mycobacterium tuberculosis L, D-transpeptidase by meropenem, a drug effective against extensively drug-resistant strains. Acta Crystallographica Section D Biological Crystallography, 69 (3), 420–431. https://doi.org/10.1107/S0907444912048998
Kohn, W., Becke, A. D., & Parr, R. G. (1996). Density functional theory of electronic structure. The Journal of Physical Chemistry, 100 (31), 12974–12980. https://doi.org/10.1021/jp960669l
Koul, A., Arnoult, E., Lounis, N., Guillemont, J., & Andries, K. (2011). The challenge of new drug discovery for tuberculosis. Nature, 469 (7331), 483–490. https://doi.org/10.1038/nature09657
Kumar, P., Arora, K., Lloyd, J. R., Lee, I. Y., Nair, V., Fischer, E., Boshoff, H. I., & Barry, C. E., III. (2012). Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium tuberculosis. Molecular Microbiology, 86 (2), 367–381. https://doi.org/10.1111/j.1365-2958.2012.08199.x
Kumar, P., Kaushik, A., Lloyd, E. P., Li, S.-G., Mattoo, R., Ammerman, N. C., Bell, D. T., Perryman, A. L., Zandi, T. A., Ekins, S., Ginell, S. L., Townsend, C. A., Freundlich, J. S., & Lamichhane, G. (2017). Non-classical transpeptidases yield insight into new antibacterials. Nature Chemical Biology, 13 (1), 54–61. https://doi.org/10.1038/nchembio.2237
Lavollay, M., Arthur, M., Fourgeaud, M., Dubost, L., Marie, A., Riegel, P., Gutmann, L., & Mainardi, J. L. (2009). The beta-lactam-sensitive D,D-carboxypeptidase activity of Pbp4 controls the L,D and D,D transpeptidation pathways in Corynebacterium jeikeium. Molecular Microbiology, 74 (3), 650–661. https://doi.org/10.1111/j.1365-2958.2009.06887.x
Lavollay, M., Arthur, M., Fourgeaud, M., Dubost, L., Marie, A., Veziris, N., Blanot, D., Gutmann, L., & Mainardi, J.-L. (2008). The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation. Journal of Bacteriology, 190 (12), 4360–4366. https://doi.org/10.1128/JB.00239-08
Lee, T.-S., Cerutti, D. S., Mermelstein, D., Lin, C., LeGrand, S., Giese, T. J., Roitberg, A., Case, D. A., Walker, R. C., & York, D. M. (2018). GPU-accelerated molecular dynamics and free energy methods in Amber18: Performance enhancements and new features. Journal of Chemical Information and Modeling, 58 (10), 2043–2050. https://doi.org/10.1021/acs.jcim.8b00462
Li, H., Robertson, A. D., & Jensen, J. H. (2005). Very fast empirical prediction and rationalization of protein pKa values. Proteins, 61 (4), 704–721. https://doi.org/10.1002/prot.20660
Macheboeuf, P., Contreras-Martel, C., Job, V., Dideberg, O., & Dessen, A. (2006). Penicillin binding proteins: Key players in bacterial cell cycle and drug resistance processes. FEMS Microbiology Reviews, 30 (5), 673–691. https://doi.org/10.1111/j.1574-6976.2006.00024.x
Mainardi, J.-L., Fourgeaud, M., Hugonnet, J.-E., Dubost, L., Brouard, J.-P., Ouazzani, J., Rice, L. B., Gutmann, L., & Arthur, M. (2005). A novel peptidoglycan cross-linking enzyme for a β-lactam-resistant transpeptidation pathway. The Journal of Biological Chemistry, 280 (46), 38146–38152. https://doi.org/10.1074/jbc.M507384200
Mainardi, J.-L., Hugonnet, J.-E., Rusconi, F., Fourgeaud, M., Dubost, L., Moumi, A. N., Delfosse, V., Mayer, C., Gutmann, L., Rice, L. B., & Arthur, M. (2007). Unexpected inhibition of peptidoglycan l, d-transpeptidase from Enterococcus faecium by the β-lactam imipenem. Journal of Biological Chemistry, 282 (42), 30414–30422. https://doi.org/10.1074/jbc.M704286200
Mainardi, J.-L., Morel, V., Fourgeaud, M., Cremniter, J., Blanot, D., Legrand, R., Fréhel, C., Arthur, M., van Heijenoort, J., & Gutmann, L. (2002). Balance between two transpeptidation mechanisms determines the expression of beta-lactam resistance in Enterococcus faecium. The Journal of Biological Chemistry, 277 (39), 35801–35807. https://doi.org/10.1074/jbc.M204319200
Meyer, E. (1992). Internal water molecules and H-bonding in biological macromolecules: A review of structural features with functional implications. Protein Science, 1 (12), 1543–1562. https://doi.org/10.1002/pro.5560011203
Moraes, G. L., Gomes, G. C., De Sousa, P. R. M., Alves, C. N., Govender, T., Kruger, H. G., Maguire, G. E., Lamichhane, G., & Lameira, J. (2015). Structural and functional features of enzymes of Mycobacterium tuberculosis peptidoglycan biosynthesis as targets for drug development. Tuberculosis, 95 (2), 95–111. https://doi.org/10.1016/j.tube.2015.01.006
Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19 (14), 1639–1662. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
Morris, G. M., Huey, R., & Olson, A. J. (2008). Using autodock for ligand‐receptor docking. Current Protocols in Bioinformatics, 24 (1), 8.14.1–8.14.40. https://doi.org/10.1002/0471250953.bi0814s24
Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30 (16), 2785–2791. https://doi.org/10.1002/jcc.21256
Nicola, G., Tomberg, J., Pratt, R., Nicholas, R. A., & Davies, C. (2010). Crystal structures of covalent complexes of β-lactam antibiotics with Escherichia coli penicillin-binding protein 5: Toward an understanding of antibiotic specificity. Biochemistry, 49 (37), 8094–8104. https://doi.org/10.1021/bi100879m
Page, M. I. (2004). Beta-sultams-mechanism of reactions and use as inhibitors of serine proteases. Accounts of Chemical Research, 37 (5), 297–303. https://doi.org/10.1021/ar0200899
Papp-Wallace, K. M., Endimiani, A., Taracila, M. A., & Bonomo, R. A. (2011). Carbapenems: Past, present, and future. Antimicrobial Agents and Chemotherapy, 55 (11), 4943–4960. https://doi.org/10.1128/AAC.00296-11
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera-a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25 (13), 1605–1612. https://doi.org/10.1002/jcc.20084
Prigozhin, D. M., Krieger, I. V., Huizar, J. P., Mavrici, D., Waldo, G. S., Hung, L.-W., Sacchettini, J. C., Terwilliger, T. C., & Alber, T. (2014). Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis. PLoS One, 9 (12), e116249. https://doi.org/10.1371/journal.pone.0116249
Ranaghan, K. E., & Mulholland, A. J. (2010). Investigations of enzyme-catalysed reactions with combined quantum mechanics/molecular mechanics (QM/MM) methods. International Reviews in Physical Chemistry, 29 (1), 65–133. https://doi.org/10.1080/01442350903495417
Reed, A. E., Curtiss, L. A., & Weinhold, F. (1988). Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chemical Reviews, 88 (6), 899–926. https://doi.org/10.1021/cr00088a005
Ribeiro, A. J., Yang, L., Ramos, M. J., Fernandes, P. A., Liang, Z.-X., & Hirao, H. (2015). Insight into enzymatic nitrile reduction: QM/MM study of the catalytic mechanism of QueF nitrile reductase. ACS Catalysis, 5 (6), 3740–3751. https://doi.org/10.1021/acscatal.5b00528
Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. (1977). Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, 23 (3), 327–341. https://doi.org/10.1016/0021-9991(77)90098-5
Sauvage, E., Kerff, F., Terrak, M., Ayala, J. A., & Charlier, P. (2008). The penicillin-binding proteins: Structure and role in peptidoglycan biosynthesis. FEMS Microbiology Reviews, 32 (2), 234–258. https://doi.org/10.1111/j.1574-6976.2008.00105.x
Schleifer, K. H., & Kandler, O. (1972). Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriological Reviews, 36 (4), 407–477. https://doi.org/10.1128/MMBR.36.4.407-477.1972
Shi, Q., Meroueh, S. O., Fisher, J. F., & Mobashery, S. (2008). Investigation of the mechanism of the cell wall DD-carboxypeptidase reaction of penicillin-binding protein 5 of Escherichia coli by quantum mechanics/molecular mechanics calculations. Journal of the American Chemical Society, 130 (29), 9293–9303. https://doi.org/10.1021/ja801727k
Shi, R., Li, W., Liu, G., & Tang, Y. (2013). Catalytic mechanism of cytochrome P450 2D6 for 4‐hydroxylation of aripiprazole: A QM/MM study. Chinese Journal of Chemistry, 31 (9), 1219–1227. https://doi.org/10.1002/cjoc.201300427
Silva, J. R. r A., Roitberg, A. E., & Alves, C. u N. (2014). Catalytic mechanism of L,D-transpeptidase 2 from Mycobacterium tuberculosis described by a computational approach: Insights for the design of new antibiotics drugs. Journal of Chemical Information and Modeling, 54 (9), 2402–2410. https://doi.org/10.1021/ci5003069
Sousa, S. F., Ribeiro, A. J., Neves, R. P., Brás, N. F., Cerqueira, N. M., Fernandes, P. A., & Ramos, M. J. (2017). Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms. Wiley Interdisciplinary Reviews: Computational Molecular Science, 7 (2), e1281.
Spratt, B. G., & Cromie, K. D. (1988). Penicillin-binding proteins of gram-negative bacteria. Reviews of Infectious Diseases, 10 (4), 699–711. https://doi.org/10.1093/clinids/10.4.699
Triboulet, S., Arthur, M., Mainardi, J.-L., Veckerlé, C., Dubée, V., NGuekam-Moumi, A., Gutmann, L., Rice, L. B., & Hugonnet, J.-E. (2011). Inactivation kinetics of a new target of beta-lactam antibiotics. The Journal of Biological Chemistry, 286 (26), 22777–22784. https://doi.org/10.1074/jbc.M111.239988
van der Kamp, M. W., & Mulholland, A. J. (2013). Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry, 52 (16), 2708–2728. https://doi.org/10.1021/bi400215w
Vollmer, W., Blanot, D., & De Pedro, M. A. (2008). Peptidoglycan structure and architecture. FEMS Microbiology Reviews, 32 (2), 149–167. https://doi.org/10.1111/j.1574-6976.2007.00094.x
Vreven, T., Byun, K. S., Komáromi, I., Dapprich, S., Montgomery, J. A., Jr., Morokuma, K., & Frisch, M. J. (2006). Combining quantum mechanics methods with molecular mechanics methods in ONIOM. Journal of Chemical Theory and Computation, 2 (3), 815–826. https://doi.org/10.1021/ct050289g
Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004). Development and testing of a general amber force field. Journal of Computational Chemistry, 25 (9), 1157–1174. https://doi.org/10.1002/jcc.20035
Waxman, D. J., & Strominger, J. L. (1983). Penicillin-binding proteins and the mechanism of action of beta-lactam antibiotics. Annual Review of Biochemistry, 52 (1), 825–869. https://doi.org/10.1146/annurev.bi.52.070183.004141
WHO. (2019). Global tuberculosis report. https://www.who.int/tb/publications/global_report/en/
Zhao, Y., & Truhlar, D. G. (2008). 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. Theoretical Chemistry Accounts, 120 (1-3), 215–241. https://doi.org/10.1007/s00214-007-0310-x
