Skip to main content
SpringerLink
Log in

Improvement of the self-consistent-charge density-functional-tight-binding theory by a modified Mulliken charge

  • Regular Article
  • Published:
Theoretical Chemistry Accounts Aims and scope Submit manuscript

Abstract

Although extensive efforts had been carried out to improve the accuracy of the self-consistent-charge density-functional-tight-binding (SCC-DFTB), the application of SCC-DFTB on biological systems (e.g., enzymes) is still limited. Our benchmark calculations show that the original SCC-DFTB/MM is not able to properly descript the human carboxylesterase 1 (CES1) catalyzed hydrolysis of d-threo-methylphenidate (dMD). In contrast to the ab initio QM/MM results, SCC-DFTB/MM underestimates the activation free energy barrier and renders the acylation process as a single-step reaction without a tetrahedral intermediate. It seems like that SCC-DFTB/MM misestimates the developing negative QM Mulliken charge of the substrate oxygen atom in the oxyanion hole. To improve the SCC-DFTB energy and the electrostatic interaction between QM (SCC-DFTB) and MM atoms, we adopt an optimization strategy for QM Mulliken charge, in which an empirical parameter is trained to fit the SCC-DFTB Mulliken charge to high-level DFT method along the reaction coordinate. Herein, the optimized Mulliken charge-based SCC-DFTB method is denoted as SCC-DFTBMR. Finally, benchmark and free energy calculations were performed to prove the applicability of SCC-DFTBMR to CES1-catalyzed reaction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gao J, Truhlar DG (2002) Quantum mechanical methods for enzyme kinetics. Annu Rev Phys Chem 53(1):467–505

    Article  CAS  Google Scholar 

  2. Senn HM, Thiel W (2006) QM/MM methods for biological systems. In: Atomistic approaches in modern biology. Springer, pp 173–290

  3. Riccardi D, Schaefer P, Yang YuH, Ghosh N, Prat-Resina X, König P, Li G, Xu D, Guo H, Elstner M, Cui Q (2006) Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes. J Phys Chem B 110(13):6458–6469

    Article  CAS  Google Scholar 

  4. Field MJ, Bash PA, Karplus M (1990) A combined quantum-mechanical and molecular mechanical potential for molecular-dynamics simulations. J Comput Chem 11(6):700–733

    Article  CAS  Google Scholar 

  5. Hu H, Yang W (2008) Free energies of chemical reactions in solution and in enzymes with AB initio QM/MM methods. Annu Rev Phys Chem 59:573–601

    Article  CAS  Google Scholar 

  6. Thiel W (2014) Semiempirical quantum–chemical methods. Wiley Interdiscip Rev Comput Mol Sci 4(2):145–157

    Article  CAS  Google Scholar 

  7. Elstner M, Porezag D, Jungnickel G, Elsner J, Haugk M, Frauenheim T, Suhai S, Seifert G (1998) Self-consistent-charge density-functional tight-binding method for simulations of complex materials properties. Phys Rev B 58(11):7260

    Article  CAS  Google Scholar 

  8. Bash PA, Field MJ, Karplus M (1987) Free energy perturbation method for chemical reactions in the condensed phase: a dynamic approach based on a combined quantum and molecular mechanics potential. J Am Chem Soc 109(26):8092–8094

    Article  CAS  Google Scholar 

  9. Yao J, Wlodawer A, Guo H (2013) Understanding the autocatalytic process of Pro-Kumamolisin activation from molecular dynamics and quantum mechanical/molecular mechanical (QM/MM) free-energy simulations. Chem Eur J 19(33):10849–10852

    Article  CAS  Google Scholar 

  10. Yao J, Guo H, Chaiprasongsuk M, Zhao N, Chen F, Yang X, Guo H (2015) Substrate-assisted catalysis in the reaction catalyzed by salicylic acid binding protein 2 (SABP2), a potential mechanism of substrate discrimination for some promiscuous enzymes. Biochemistry 54(34):5366–5375

    Article  CAS  Google Scholar 

  11. Yao J, Yuan Y, Zheng F, Zhan C-G (2016) Unexpected reaction pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin. Sci Rep 6:22322

    Article  CAS  Google Scholar 

  12. Cui Q, Elstner M (2014) Density functional tight binding: values of semi-empirical methods in an ab initio era. PCCP 16(28):14368–14377

    Article  CAS  Google Scholar 

  13. Zheng G, Niklasson AMN, Karplus M (2011) Lagrangian formulation with dissipation of Born-Oppenheimer molecular dynamics using the density-functional tight-binding method. J Chem Phys 135(4):044122

    Article  Google Scholar 

  14. Elstner M, Hobza P, Frauenheim T, Suhai S, Kaxiras E (2001) Hydrogen bonding and stacking interactions of nucleic acid base pairs: a density-functional-theory based treatment. J Chem Phys 114(12):5149–5155

    Article  CAS  Google Scholar 

  15. Yang Y, Yu H, York D, Elstner M, Cui Q (2008) Description of phosphate hydrolysis reactions with the self-consistent-charge density-functional-tight-binding (SCC-DFTB) theory. 1. Parameterization. J Chem Theory Comput 4(12):2067–2084

    Article  CAS  Google Scholar 

  16. Hou G, Zhu X, Elstner M, Cui Q (2012) A modified QM/MM hamiltonian with the self-consistent-charge density-functional-tight-binding theory for highly charged QM regions. J Chem Theory Comput 8(11):4293–4304

    Article  CAS  Google Scholar 

  17. Gaus M, Cui Q, Elstner M (2011) DFTB3: extension of the self-consistent-charge density-functional tight-binding method (SCC-DFTB). J Chem Theory Comput 7(4):931–948

    Article  CAS  Google Scholar 

  18. Gaus M, Lu X, Elstner M, Cui Q (2014) Parameterization of DFTB3/3OB for sulfur and phosphorus for chemical and biological applications. J Chem Theory Comput 10:1518–1537

    Article  CAS  Google Scholar 

  19. Christensen AS, Elstner M, Cui Q (2015) Improving intermolecular interactions in DFTB3 using extended polarization from chemical-potential equalization. J Chem Phys 143(8):084123

    Article  Google Scholar 

  20. Yao J, Xu Q, Chen F, Guo H (2010) QM/MM free energy simulations of salicylic acid methyltransferase: effects of stabilization of TS-like structures on substrate specificity. J Phys Chem B 115(2):389–396

    Article  Google Scholar 

  21. Xu Q, Yao J, Wlodawer A, Guo H (2011) Clarification of the mechanism of acylation reaction and origin of substrate specificity of the serine-carboxyl peptidase sedolisin through QM/MM free energy simulations. J Phys Chem B 115(10):2470–2476

    Article  CAS  Google Scholar 

  22. Yao J, Nellas RB, Glover MM, Shen T (2011) Stability and sugar recognition ability of ricin-like carbohydrate binding domains. Biochemistry 50(19):4097–4104

    Article  CAS  Google Scholar 

  23. Chu Y, Yao J, Guo H (2012) QM/MM MD and free energy simulations of G9a-like protein (GLP) and its mutants: understanding the factors that determine the product specificity. PLoS ONE 7(5):e37674

    Article  CAS  Google Scholar 

  24. Yao J, Chu Y, An R, Guo H (2012) Understanding product specificity of protein lysine methyltransferases from QM/MM molecular dynamics and free energy simulations: the effects of mutation on SET7/9 beyond the Tyr/Phe switch. J Chem Inf Model 52(2):449–456

    Article  CAS  Google Scholar 

  25. Yao J, Xu Q, Guo H (2013) QM/MM and free-energy simulations of deacylation reaction catalysed by sedolisin, a serine-carboxyl peptidase. Mol Simul 39(3):206–213

    Article  CAS  Google Scholar 

  26. Sun Z, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q, Hurley TD, Bosron WF (2004) Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther 310(2):469–476

    Article  CAS  Google Scholar 

  27. Cui Q, Elstner M, Kaxiras E, Frauenheim T, Karplus M (2000) A QM/MM implementation of the self-consistent charge density functional tight binding (SCC-DFTB) method. J Phys Chem B 105(2):569–585

    Article  Google Scholar 

  28. Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR (2003) Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Mol Biol 10(5):349–356

    Article  CAS  Google Scholar 

  29. Brünger AT, Karplus M (1988) Polar hydrogen positions in proteins: empirical energy placement and neutron diffraction comparison. Proteins: Struct, Funct, Bioinf 4(2):148–156

    Article  Google Scholar 

  30. Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30(10):1545–1614

    Article  CAS  Google Scholar 

  31. Jorgensen WL (1981) Quantum and statistical mechanical studies of liquids. 10. Transferable intermolecular potential functions for water, alcohols, and ethers—application to liquid water. J Am Chem Soc 103(2):335–340

    Article  CAS  Google Scholar 

  32. Neria E, Fischer S, Karplus M (1996) Simulation of activation free energies in molecular systems. J Chem Phys 105(5):1902–1921

    Article  CAS  Google Scholar 

  33. Cui Q, Elstner M, Kaxiras E, Frauenheim T, Karplus M (2001) A QM/MM implementation of the self-consistent charge density functional tight binding (SCC-DFTB) method. J Phys Chem B 105(2):569–585

    Article  CAS  Google Scholar 

  34. MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102(18):3586–3616

    Article  CAS  Google Scholar 

  35. Huang J, MacKerell AD (2013) CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J Comput Chem 34(25):2135–2145

    Article  CAS  Google Scholar 

  36. Brooks CL, Brunger A, Karplus M (1985) Active-site dynamics in protein molecules: a stochastic boundary molecular-dynamics approach. Biopolymers 24(5):843–865

    Article  CAS  Google Scholar 

  37. Ryckaert JP, Ciccotti G, Berendsen HJC (1977) Numerical-integration of cartesian equations of motion of a system with constraints—molecular-dynamics of N-alkanes. J Comput Phys 23(3):327–341

    Article  CAS  Google Scholar 

  38. Elstner M (2006) The SCC-DFTB method and its application to biological systems. Theor Chem Acc 116(1–3):316–325

    Article  CAS  Google Scholar 

  39. Shao Y, Gan Z, Epifanovsky E, Gilbert ATB, Wormit M, Kussmann J, Lange AW, Behn A, Deng J, Feng X, Ghosh D, Goldey M, Horn PR, Jacobson LD, Kaliman I, Khaliullin RZ, Kuś T, Landau A, Liu J, Proynov EI, Rhee YM, Richard RM, Rohrdanz MA, Steele RP, Sundstrom EJ, Woodcock HL, Zimmerman PM, Zuev D, Albrecht B, Alguire E, Austin B, Beran GJO, Bernard YA, Berquist E, Brandhorst K, Bravaya KB, Brown ST, Casanova D, Chang C-M, Chen Y, Chien SH, Closser KD, Crittenden DL, Diedenhofen M, DiStasio RA, Do H, Dutoi AD, Edgar RG, Fatehi S, Fusti-Molnar L, Ghysels A, Golubeva-Zadorozhnaya A, Gomes J, Hanson-Heine MWD, Harbach PHP, Hauser AW, Hohenstein EG, Holden ZC, Jagau T-C, Ji H, Kaduk B, Khistyaev K, Kim J, Kim J, King RA, Klunzinger P, Kosenkov D, Kowalczyk T, Krauter CM, Lao KU, Laurent AD, Lawler KV, Levchenko SV, Lin CY, Liu F, Livshits E, Lochan RC, Luenser A, Manohar P, Manzer SF, Mao S-P, Mardirossian N, Marenich AV, Maurer SA, Mayhall NJ, Neuscamman E, Oana CM, Olivares-Amaya R, O’Neill DP, Parkhill JA, Perrine TM, Peverati R, Prociuk A, Rehn DR, Rosta E, Russ NJ, Sharada SM, Sharma S, Small DW, Sodt A, Stein T, Stück D, Su Y-C, Thom AJW, Tsuchimochi T, Vanovschi V, Vogt L, Vydrov O, Wang T, Watson MA, Wenzel J, White A, Williams CF, Yang J, Yeganeh S, Yost SR, You Z-Q, Zhang IY, Zhang X, Zhao Y, Brooks BR, Chan GKL, Chipman DM, Cramer CJ, Goddard WA, Gordon MS, Hehre WJ, Klamt A, Schaefer HF, Schmidt MW, Sherrill CD, Truhlar DG, Warshel A, Xu X, Aspuru-Guzik A, Baer R, Bell AT, Besley NA, Chai J-D, Dreuw A, Dunietz BD, Furlani TR, Gwaltney SR, Hsu C-P, Jung Y, Kong J, Lambrecht DS, Liang W, Ochsenfeld C, Rassolov VA, Slipchenko LV, Subotnik JE, Van Voorhis T, Herbert JM, Krylov AI, Gill PMW, Head-Gordon M (2015) Advances in molecular quantum chemistry contained in the Q-Chem 4 program package. Mol Phys 113(2):184–215

    Article  CAS  Google Scholar 

  40. Woodcock HL, Hodošček M, Gilbert AT, Gill PM, Schaefer HF, Brooks BR (2007) Interfacing Q-Chem and CHARMM to perform QM/MM reaction path calculations. J Comput Chem 28(9):1485–1502

    Article  CAS  Google Scholar 

  41. Torrie GM, Valleau JP (1974) Monte-Carlo free-energy estimates using non-Boltzmann sampling—application to subcritical Lennard–Jones fluid. Chem Phys Lett 28(4):578–581

    Article  CAS  Google Scholar 

  42. Kumar S, Bouzida D, Swendsen RH, Kollman PA, Rosenberg JM (1992) The weighted histogram analysis method for free-energy calculations on biomolecules. 1. The method. J Comput Chem 13(8):1011–1021

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China with Grant 21703079 and the Shandong Provincial Natural Science Foundation, China with Grants ZR2017BB056 and ZR2017QD013.

Author information

Authors and Affiliations

  1. School of Biological Science and Technology, University of Jinan, Jinan, 250022, People’s Republic of China

    Xia Wang & Jianzhuang Yao

Authors
  1. Xia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianzhuang Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianzhuang Yao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Yao, J. Improvement of the self-consistent-charge density-functional-tight-binding theory by a modified Mulliken charge. Theor Chem Acc 136, 124 (2017). https://doi.org/10.1007/s00214-017-2156-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00214-017-2156-1

Keywords

Search

Navigation