Abstract
Quantum mechanical (QM) semiempirical methods (SMs), combined with molecular mechanics (MM) force fields, are extensively used in theoretical studies of enzymatic reactions. Despite being several orders of magnitude faster than ab initio methods, their correctness is essential to be used in calculations requiring statistical simulations. Herein, a wide range of SMs are examined, from those based on s and p orbitals, sp-SMs (MNDO, AM1, PM3 and RM1), to those including d orbitals, spd-SMs, either based on approximations to the Hartree–Fock theory (MNDO/d, PM6 and AM1/d-PhoT) or derived from density functional theory (DFTB3). These QM Hamiltonians are used within a multiscale QM/MM additive scheme, to clarify their usefulness in mechanistic studies of phosphoryl-transfer reactions. The SN2-like reaction of the adenylyl group transfer catalysed by 4′-O-Nucleotidyltransferase (ANT4′) was selected as a benchmark. Geometrical characteristics of stationary structures, the shape of potential energy surfaces together with the barrier heights and kinetic isotope effects (KIEs), obtained with the different SMs/MM methods were compared with results obtained at higher M06-2X/MM level of theory. Critical limitations of the sp-SMs in the present mechanistic study were detected. The spd-SMs describe the reaction as a concerted process, same as the reference method M06-2X, but none of them is free of limitations. PM6 reproduces the biased trend of previous sp-SMs stabilizing structures of phosphorous atoms with certain pentavalent character, while AM1/d-PhoT and DFTB3 describe TSs more dissociative than M06-2X, which determines the lower quality of the computed primary and secondary 16O/18O KIEs. Efforts to improve the SMs can be guided by the exposure of their limitations, which were supported by the results of a second studied phosphoryl-transfer reactions; the hydrolysis of phosphodiester bond at the 3′-end of the viral DNA (vDNA). Thus, for instance, further increases in SMs accuracy can be achieved by improving the training and survey reference data sets, a more complete set of parameters for describing intermolecular interactions or further developments of spd-SMs.
Similar content being viewed by others
References
Masgrau L, Truhlar DG (2015) Acc Chem Res 48:431–438
Świderek K, Tuñón I, Moliner V (2014) WIREs Comput Mol Sci 4:407–421
Świderek K, Ruiz-Pernía JJ, Moliner V, Tuñón I (2014) Curr Opin Chem Biol 21:11–18
Mlyńsky V, Banaś P, Šponer J, van der Kamp MW, Mulholland AJ, Otyepka M (2014) J Chem Theory Comput 10:1608–1622
Krzemińska A, Moliner V, Świderek K (2016) J Am Chem Soc 138:16283–16298
Higashi M, Truhlar DG (2009) J Chem Theory Comput 5:2925–2929
Singh UC, Kollman PA (1986) J Comput Chem 7:718–730
Warshel A, Levitt M (1976) J Mol Biol 103:227–249
Martí S, Andrés J, Moliner V, Silla E, Tuñón I, Bertrán J (2008) J Am Chem Soc 130:2894–2895
Martí S, Andrés J, Moliner V, Silla E, Tuñón I, Bertrán J (2009) J Am Chem Soc 131:16156–16161
Świderek K, Tuñón I, Williams IH, Moliner V (2018) J Am Chem Soc 140:4327–4334
Świderek K, Martí S, Moliner V (2014) ACS Catal 4:426–434
Świderek K, Tuñón I, Martí S, Moliner V (2015) ACS Catal 5:1172–1185
Doron D, Major DT, Kohen A, Thiel W, Wu X (2011) J Chem Theory Comput 7:3420–3437
Vardi-Kilshtain A, Major DT, Kohen A, Engel H, Doron D (2012) J Chem Theory Comput 8:4786–4796
Major DT, Nam K, Gao J (2006) J Am Chem Soc 128:8114–8115
Liu CT, Layfield JP, Stewart RJ III, French JB, Hanoian P, Asbury JB, Hammes-Schiffer S, Benkovic SJ (2014) J Am Chem Soc 136:10349–10360
Świderek K, Arafet K, Kohen A, Moliner V (2017) J Chem Theory Comput 13:1375–1388
Lopez-Canut V, Roca M, Bertran J, Moliner V, Tuñón I (2011) J Am Chem Soc 133:12050–12062
Christensen AS, Kubař T, Cui Q, Elstner M (2016) Chem Rev 116:5301–5337
Petrovic D, Szeler K, Kamerlin SCL (2018) Chem Commun 54:3077–3089
Bordes I, García-Junceda E, Sánchez-Moreno I, Castillo R, Moliner V (2017) Int J Quantum Chem 118:e25520
Lopez-Canut V, Roca M, Bertran J, Moliner V, Tuñón I (2010) J Am Chem Soc 132:6955–6963
Nam K, Cui Q, Gao J, York DM (2007) J Chem Theory Comput 3:486–504
Arantes GM, Loos M (2006) Phys Chem Chem Phys 8:347–353
Lopez X, York DM (2001) Theo Chem Acc 109:149–159
Yang Y, Yu H, York D, Elstner M, Cui Q (2008) J Chem Theory Comput 4:2067–2084
Marcos E, Anglada JM, Crehuet R (2008) Phys Chem Chem Phys 10:2442–2450
Marcos E, Field MJ, Crehuet R (2010) Proteins 78:2405–2411
Murillo-López J, Zinovjev K, Pereira H, Caniuguir A, Garratt R, Babul J, Recabarren R, Alzate-Morales J, Caballero J, Tuñón I, Cabrera R (2019) Chem Sci 10:2882–2892
Dewar MJS, Thiel W (1977) J Am Chem Soc 99:4899–4907
Dewar MJS, Zoebisch EG, Healy EF, Stewart JJP (1985) J Am Chem Soc 107:3902–3909
Stewart JJP (1989) J Comput Chem 10:209–221
Rocha GB, Oliveira Freire R, Simas AM, Stewart JJP (2006) J Comput Chem 27:1101–1111
Thiel W, Voityuk AA (1992) Theor Chim Acta 81:391–404
Thiel W, Voityuk AA (1996) J Phys Chem 100:616–626
Bernal-Uruchurtu MI, Martins-Costa MTC, Millot C, Ruiz-López MF (2000) J Comput Chem 21:572–581
Bernal-Uruchurtu MI, Ruiz-López MF (2000) Chem Phys Lett 330:118–124
Harb W, Bernal-Uruchurtu MI, Ruiz-López MF (2004) Theor Chem Acc 112:204–216
Arillo-Flores OI, Ruiz-López MF, Bernal-Uruchurtu MI (2007) Theor Chem Acc 118:425–435
Stewart JJP (2007) J Mol Model 13:1173–1213
Stewart JJP (2009) J Mol Model 15:765–805
Marion A, Monard G, Ruiz-López MF, Ingrosso F (2014) J Chem Phys 141:034106
Imhof P, Noé F, Fischer S, Smith JC (2006) J Chem Theory Comput 2:1050–1056
Wahiduzzaman M, Oliveira AF, Philipsen P, Zhechkov L, van Lenthe E, Witek H, Heine T (2013) J Chem Theory Comput 9:4006–4017
Gaus M, Lu X, Elstner M, Cui Q (2014) J Chem T Theory Comput 10:1518–1537
Gaus M, Goez A, Elstner M (2013) J Chem Theory Comput 9:338–354
Gaus M, Cui Q (2012) Elstner. J Chem Theory Comput 7:931–948
Editorial (2013) The antibiotic alarm. Nature 495:141
Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F et al (2015) Nat Rev Microbiol 13:310–317
Becker B, Matthew A (2013) ACS Chem Biol 8:105–115
Martí S, Bastida A, Świderek K (2019) Front Chem 6:660
Zhao Y, Truhlar DG (2008) Acc Chem Res 41:157–167
Zhao Y, Truhlar DG (2008) Theor Chem Acc 120:215–241
Bordes I, Ruiz-Pernía JJ, Castillo R, Moliner V (2015) Org Biomol Chem 13:10179–10190
Bordes I, Castillo R, Moliner V (2017) J Phys Chem B 121:8878–8892
Pedersen LC, Benning MM, Holden HM (1995) Biochemistry 34:13305–13311
Olsson MHM, Sondergaard CR, Rostkowski M, Jensen JH (2011) J Chem Theory Comput 7:525–537
Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Kollman P et al (2003) J Comput Chem 24:1999–2012
Field MJ, Albe M, Bret C, Proust-De Martin F, Thomas A (2000) J Comput Chem 21:1088–1100
Krzemińska A, Paneth P, Moliner V, Świderek K (2015) J Phys Chem B 119:917–927
Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79:926–935
Stewart JJP (1996) Quantum Chem Progr Exch 455:6
Case DA, Betz RM, Cerutti DS, Cheatham TE III, Darden TA, Duke RE, Giese TJ, Gohlke H, Goetz AW, Homeyer N, Izadi S, Janowski P, Kaus J, Kovalenko A, Lee TS, LeGrand S, Li P, Lin C, Luchko T, Luo R, Madej B, Mermelstein D, Merz KM, Monard G, Nguyen H, Nguyen HT, Omelyan I, Onufriev A, Roe DR, Roitberg A, Sagui C, Simmerling CL, Botello-Smith WM, Swails J, Walker RC, Wang J, Wolf RM, Wu X, Xiao L, Kollman PA (2016) AMBER 2016. University of California, San Francisco
Byrd RH, Lu P, Nocedal J, Zhu C (1995) J Sci Comput 16:1190–1208
Baker J, Kessi A, Delley BJ (1996) Chem Phys 105:192–212
Baker J (1997) J Comput Chem 18:1079–1095
Martí S, Moliner V, Tuñón I, Williams IH (2005) J Phys Chem B 109:3707–3710
Martí S, Moliner V, Tuñón I (2005) J Chem Theory Comput 1:1008–1016
Fukui K (1981) Acc Chem Res 14:363–368
Świderek K, Martí S, Tuñón I, Moliner V, Bertran J (2015) J Am Chem Soc 137:12024–12034
Tubert-Brohman I, Guimaraes CRW, Jorgensen WL (2005) J Chem Theory Comput 1:817–823
Lopez X, York DM (2003) Theor Chem Acc 109:149–159
Gregersen BA, Lopez X, York DM (2003) J Am Chem Soc 125:7178–7179
Gregersen BA, Lopez X, York DM (2004) J Am Chem Soc 126:7504–7513
Jencks WP (1985) Chem Rev 85:511–527
O’Ferrall RM (1970) J Chem Soc B 274–277
Gaus M, Lu X, Elstner M, Cui Q (2014) J Chem Theor Comput 10:1518–1537
Turner JA, Moliner V, Williams IH (1999) Phys Chem Chem Phys 1:1323–1331
Ferrer S, Tuñón I, Martí S, Moliner V, García-Viloca M, González-Lafont A, Lluch JM (2006) J Am Chem Soc 128:16851–16863
Xue Q, Yeung ES (1995) Nature 373:681–683
Gerratana B, Cleland WW, Reinhardt LA (2001) Biochemistry 40:2964–2971
Kaminski S, Gaus M, Elstner M (2012) J Phys Chem A 116:11927–11937
Kaminski S, Giese TJ, Gaus M, York DM, Elstner M (2012) J Phys Chem A 116:9131–9141
Krzemińska A, Świderek K (2019) J Chem Inf Model 59:2995–3005
Acknowledgements
This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (Grant PGC2018-094852-B-C21), Universitat Jaume I (Project UJI B2017- 31). KŚ thanks the MINECO for a Juan de la Cierva—Incorporación (Ref. IJCI-2016-27503) contract. Authors acknowledge computational resources from the Servei d’Informàtica of Universitat Jaume I.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Published as part of the special collection of articles derived from the 11th Congress on Electronic Structure: Principles and Applications (ESPA-2018).
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Martí, S., Moliner, V. & Świderek, K. Examination of the performance of semiempirical methods in QM/MM studies of the SN2-like reaction of an adenylyl group transfer catalysed by ANT4′. Theor Chem Acc 138, 120 (2019). https://doi.org/10.1007/s00214-019-2507-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00214-019-2507-1