PERTANIKA JOURNAL OF SCIENCE AND TECHNOLOGY

 

e-ISSN 2231-8526
ISSN 0128-7680

Home / Regular Issue / JST Vol. 31 (6) Oct. 2023 / JST-3967-2022

 

Effect of Scaling the Electrostatic Interactions on the Free Energy of Transfer of Azurin from Water to Lipid Membrane Determined by Coarse-Grained Simulations

Dian Fitrasari, Acep Purqon and Suprijadi

Pertanika Journal of Science & Technology, Volume 31, Issue 6, October 2023

DOI: https://doi.org/10.47836/pjst.31.6.06

Keywords: Coarse-Grained MARTINI method, electrostatic scaling, free energy analysis, protein-lipid membrane model, windows separation

Published on: 12 October 2023

Azurin protein potentially plays an important role as an anti-cancer therapeutic agent, particularly in treating breast cancer in experiments and showing without having a negative effect on normal cells. Although the interaction mechanism between protein and lipid membrane is complicated, it can be modeled as protein-lipid interaction. Since the all-atom (AA) model simulation is cost computing, we apply a coarse-grained (CG-MARTINI) model to calculate the protein-lipid interaction. We investigate the binding free energy value dependency by varying the windows separation and electrostatic scale parameters. After scaling the electrostatic interactions by a factor of 0.04, the best result in terms of free energy is -140.831 kcal/mol, while after window-separation optimization, it reaches -71.859 kcal/mol. This scaling was necessary because the structures from the CG MARTINI model have a higher density than the corresponding all-atom structures. We thus postulate that electrostatic interactions should be scaled down in this case of CG-MARTINI simulations.

  • Adman, E. T., & Jensen, L. H. (1981). Structural features of Azurin at 2.7 angstroms resolution. Israel Journal of Chemistry, 21(1), 8-12. https://doi.org/10.1002/ijch.198100003

  • Arumugam, S., Chwastek, G., & Schwille, P. (2011). Protein–membrane interactions: The virtue of minimal systems in systems biology. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 3(3), 269-280. https://doi.org/10.1002/wsbm.119

  • Beveridge, D. L., & DiCapua, F. M. (1989). Free energy via molecular simulation: Applications to chemical and biomolecular systems. Annual Review of Biophysics and Biophysical Chemistry, 18(1), 431-492. https://doi.org/10.1146/annurev.bb.18.060189.002243

  • Frauenfelder, H., Chena, G., Berendzena, J., Fenimorea, P. W., Janssonb, H., McMahona, B. H., Stroec, I. R., Swensond, J., & Younge, R. D. (2009). A unified model of protein dynamics. Proceedings of the National Academy of Sciences, 106(13), 5129-5134. https://doi.org/10.1073/pnas.0900336106

  • Gumbart, J., & Roux B. (2012). Determination of membrane-insertion free energies by molecular dynamics simulations. Biophysical Journal, 102(4), 795-801. https://doi.org/10.1016/j.bpj.2012.01.021

  • Gumbart J., Chipot C., & Schultena K. (2011). Free-energy cost for translocon-assisted insertion of membrane proteins. Proceedings of the National Academy of Sciences, 108(9), 3596-3601. https://doi.org/10.1073/pnas.1012758108

  • Gurtovenko, A. A., & Anwar, J. (2009). Interaction of ethanol with biological membranes: The formation of non- bilayer structures within the membrane interior and their significance. Journal of Physical Chemistry B, 2009, 113(7), 1983-1992. https://doi.org/10.1021/jp808041z

  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD-visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33-38. https://doi.org/10.1016/0263-7855(96)00018-5.

  • Jiang, W., Hodoscek, M., & Roux, B. (2009). Computation of absolute hydration and binding free energy with free energy perturbation distributed replica-exchange molecular dynamics (FEP/REMD). Journal of Chemical Theory and Computation, 5(10), 2583-2588. https://doi.org/10.1021/ct900223z.

  • Kucerka, N., Tristram-Nagle, S., & Nagle, J. F. (2006). Structure of fully hydrated fluid phase lipid bilayers with monounsaturated chains. Journal of Membrane Biology, 208(3), 193-202. https://doi: 10.1007/s00232-005-7006-8.

  • Kurniawan, I., Kawaguchi, K., Sugimori, K., Sakurai, T., & Nagao, H. (2019). Theoretical studies on electronic structure and proteins of type I copper center in copper proteins. Science Report Kanazawa University, 63, 1-13.

  • Li, Y., & Nam, K. (2020). Repulsive soft-core potentials for efficient alchemical free energy calculations. Journal of Chemical Theory and Computation, 16(8), 4776-4789. https://doi:10.1021/acs.jctc.0c00163.

  • Marrink, S. J., Risselada, H. J., Yefimov, S., Tieleman, D. P., & De Vries, A. H. (2007). The MARTINI force field: Coarse-grained model for biomolecular simulations. Journal of Physical Chemistry B, 111(27), 7812-7824. https://doi.org/10.1021/jp071097f

  • Mark, A. E. (1998). Free energy perturbation calculations. In P. V. R. Schleyer, N. L. Allinger, T. Clark, J. Gasteiger, P. A. Kollman, H. F. Schaefer & P. R. Schreiner (Eds.), Encyclopedia of Computational Chemistry (pp.1070-1083). Wiley and Sons.

  • Pappalardo, M., Milardi, D., Grasso, D. M., & La Rosa, C. (2003). Free energy perturbation and molecular dynamics calculations of copper binding to Azurin. Journal of Computational Chemistry, 24(6), 779-785. https://doi.org/10.1002/jcc.10213

  • Phillips, J. C., Hardy, D. J., Maia, J. D. C., Stone, J. E., Ribeiro, J. V., Bernardi, R. C., Buch, R., Fiorin, G., Henin, J., Jiang, W., McGreevy, R., Melo, M. C. R., Radak, B. K., Skeel, R. D., Singharoy, A., Wang, Y., Roux, B., Aksimentiev, A. Luthey-Schulten, Z., … & Tajkhorshid, E. (2020). Scalable molecular dynamics on CPU and GPU architectures with NAMD. Journal of Chemical Physics, 153(4), Article 044130. https://doi.org/10.1063/5.0014475

  • Pohorille, A., Jarzynski, C., & Chipot, C. (2010). Good practices in free-energy calculations. Journal of Physical Chemistry B, 114(32), 10235-10253. https://doi.org/10.1021/jp102971x.

  • Pozdnyakova, I., Guidry, J., & Wittung-Stafshede, P. (2002). Studies of pseudomonas aeruginosa Azurin mutants: Cavities in β-barrel do not affect refolding speed. Biophysical Journal, 82(5), 2645-2651. https://doi.org/10.1016/S0006-3495(02)75606-3

  • Pozdnyakova, I., & Wittung-Stafshede, P. (2001). Copper binding before polypeptide folding speeds up the formation of active (holo) Pseudomonas aeruginosa Azurin. Biochemistry, 40(45), 13728-13733. https://doi.org/10.1021/bi011591o

  • Zhu, F., Bourguet, F. A., Bennett, W. F. D., Lau, E. Y., Arrildt, K. T., Segelke, B. W., Zemla, A. T., Desautels, T. A., & Faissol, D. M. (2022). Large scale application of free energy perturbation calculations for antibody design. Scientific Reports, 12, Article 12489, https://doi.org/10.1038/s41598-022-14443-z