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Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds

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Abstract

Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds. The influence of explicit solvent is also shown to be crucial to determine the flexibility of cisplatin in quantum dynamics simulations. Two empirical topologies of cisplatin were produced by fitting its atomic fluctuations against QD in vacuum and QD with explicit first solvation shell of water molecules respectively. A third topology built in a standard way from the static optimized structure was used for comparison. The later one leads to an excessively rigid molecule and exhibits much smaller fluctuations of the bonds and angles than QD reveals. It is shown that accounting for the high flexibility of cisplatin molecule is needed for adequate description of its first hydration shell. MD simulations with flexible QD-based topology also reveal a significant decrease of the barrier of passive diffusion of cisplatin accross the model lipid bilayer. These results confirm that flexibility of organometallic compounds is an important feature to be considered in classical molecular dynamics topologies. Proposed methodology based on QD simulations provides a systematic way of building such topologies.

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References

  1. Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4(4):307–320

    Article  CAS  Google Scholar 

  2. Siddik ZH (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22(47):7265–7279

    Article  CAS  Google Scholar 

  3. Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7(8):573–584

    Article  CAS  Google Scholar 

  4. Bourgaux C, Couvreur P (2014) Interactions of anticancer drugs with biomembranes: what can we learn from model membranes? J Control Release 190:127–138

    Article  CAS  Google Scholar 

  5. Nierzwicki L, Wieczor M, Censi V, Baginski M, Calucci L, Samaritani S, Czub J, Forte C (2015) Interaction of cisplatin and two potential antitumoral platinum(ii) complexes with a model lipid membrane: a combined NMR and MD study. Phys Chem Chem Phys 17(2):1458–1468

    Article  CAS  Google Scholar 

  6. Jamieson ER, Lippard SJ (1999) Structure, recognition, and processing of cisplatin − DNA adducts. Chem Rev 99(9):2467–2498

    Article  CAS  Google Scholar 

  7. Carloni P, Sprik M, Andreoni W (2000) Key steps of the cis-platin-DNA interaction: density functional theory-based molecular dynamics simulations. J Phys Chem B 104(4):823–835

    Article  CAS  Google Scholar 

  8. Spiegel K, Rothlisberger U, Carloni P (2004) Cisplatin binding to DNA oligomers from hybrid car-parrinello/molecular dynamics simulations. J Phys Chem B 108(8):2699–2707

    Article  CAS  Google Scholar 

  9. Sharma S, Gong P, Temple B, Bhattacharyya D, Dokholyan N, Chaney S (2007) Molecular dynamic simulations of cisplatin- and oxaliplatin-d(GG) intrastand cross-links reveal differences in their conformational dynamics. J Mol Biol 373(5):1123–1140

    Article  CAS  Google Scholar 

  10. Yao S, Plastaras JP, Marzilli LG (1994) A molecular mechanics AMBER-type force field for modeling platinum complexes of guanine derivatives. Inorg Chem 33(26):6061–6077

    Article  CAS  Google Scholar 

  11. Scheeff ED, Briggs JM, Howell SB (1999) Molecular modeling of the intrastrand guanine-guanine DNA adducts produced by cisplatin and oxaliplatin. Mol Pharmacol 56(3):633–643

    Article  CAS  Google Scholar 

  12. Dodoff N (2012) A DFT/ECP-small basis set modelling of cisplatin: molecular structure and vibrational spectrum. Comput Mol Biosci 2(2):35–44

    Article  Google Scholar 

  13. Melchior A, Tolazzi M, Martínez JM, Pappalardo R, Sanchez Marcos M (2015) Hydration of two cisplatin aqua-derivatives studied by quantum mechanics and molecular dynamics simulations. J Chem Theory Comput 11(4):1735–1744

    Article  CAS  Google Scholar 

  14. Lopes JF, de A Menezes VF, Duarte HA, Rocha WR, De Almeida WB, Dos Santos HF (2006) Monte Carlo simulation of cisplatin molecule in aqueous solution. J Phys Chem B 110(24):12047–12054

    Article  CAS  Google Scholar 

  15. Paschoal D, Marcial BL, Fedoce Lopes J, De Almeida WD, Dos Santos HF (2012) The role of the basis set and the level of quantum mechanical theory in the prediction of the structure and reactivity of cisplatin. J Comp Chem 33(29):2292–2302

    Article  CAS  Google Scholar 

  16. Seminario JM (1996) Calculation of intramolecular force fields from second-derivative tensors. Int J Quantum Chem 60(7):1271–1277

    Article  Google Scholar 

  17. Sousa da Silva A, Vranken W (2012) ACPYPE - AnteChamber PYthon Parser interfacE. BMC Res Notes 5(1):367

    Article  Google Scholar 

  18. Schlegel HB, Iyengar SS, Li X, Millam JM, Voth GA, Scuseria GE, Frisch MJ (2002) Ab initio molecular dynamics: propagating the density matrix with gaussian orbitals. III. Comparison with born–oppenheimer dynamics. J Chem Phys 117(19):8694–8704

    Article  CAS  Google Scholar 

  19. Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105(8):2999–3093

    Article  CAS  Google Scholar 

  20. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81(8):3684–3690

    Article  CAS  Google Scholar 

  21. Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014101

    Article  Google Scholar 

  22. Páll S, Hess B (2013) A flexible algorithm for calculating pair interactions on SIMD architectures. Comput Phys Commun 184(12):2641–2650

    Article  Google Scholar 

  23. Van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: fast, flexible and free. J Comp Chem 26:1701–1718

  24. Yesylevskyy SO (2012) Pteros: fast and easy to use open-source C++ library for molecular analysis. J Comput Chem 33(19):1632–1636

    Article  CAS  Google Scholar 

  25. Yesylevskyy SO (2015) Pteros 2.0: evolution of the fast parallel molecular analysis library for C++ and python. J Comput Chem 36(19):1480–1488

    Article  CAS  Google Scholar 

  26. Jämbeck JPM, Lyubartsev AP (2012) An extension and further validation of an all-atomistic force field for biological membranes. J Chem Theory Comput 8(8):2938–2948

    Article  Google Scholar 

  27. Frisch MJ et al. (2009) Gaussian 09. Gaussian, Inc, Wallingford

  28. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24(16):1999–2012

    Article  CAS  Google Scholar 

  29. Hess B, Kutzner C, van der Spoel David, Lindhal E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4(3):435–447

    Article  CAS  Google Scholar 

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Correspondence to Christophe Ramseyer.

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Yesylevskyy, S., Cardey, B., Kraszewski, S. et al. Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds. J Mol Model 21, 268 (2015). https://doi.org/10.1007/s00894-015-2812-0

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  • DOI: https://doi.org/10.1007/s00894-015-2812-0

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