Skip to main content
SpringerLink
Log in

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation

  • Original Paper
  • Published:
Journal of Biological Physics Aims and scope Submit manuscript

Abstract

Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17β-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.

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
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Salis, A., Ninhamb, B.W.: Models and mechanisms of Hofmeister effects in electrolyte solutions, and colloid and protein systems revisited. Chem. Soc. Rev. 43, 7358–7377 (2014)

    Article  Google Scholar 

  2. Hille, B.: Ion Channels of Excitable Membranes. Sinauer Associates, Sunderland (2001)

    Google Scholar 

  3. Kramer, R.M., Shende, V.R., Motl, N., Pace, C.N., Scholtz, J.M.: Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility. Biophys. J. 102, 1907–1915 (2012)

    Article  ADS  Google Scholar 

  4. Peggion, E., Mammi, S., Palumbo, M., Moroder, L., Wünsch, E.: Interaction of calcium ions with peptide hormones of the gastrin family. Biopolymers 22, 2443–2457 (1983)

    Article  Google Scholar 

  5. Saboury, A.A., Atri, M.S., Sanati, M.H., Moosavi-Movahedi, A.A., Hakimelahi, G.H., Sadeghi, M.: A thermodynamic study on the interaction between magnesium ion and human growth hormone. Biopolymers 81, 120–126 (2006)

    Article  Google Scholar 

  6. Gould, K.G., Ansari, A.H.: Electrolyte interactions in cervical mucus and their relationship to circulating hormone levels. Contraception 23, 507–516 (1981)

    Article  Google Scholar 

  7. van Gunsteren, W.F., Mark, A.E.: On the interpretation of biochemical data by molecular dynamics computer simulation. Eur. J. Biochem. 204, 947–961 (1992)

    Article  Google Scholar 

  8. Santos, E.S., Souza, L.C., Assis, P.N., Almeida, P.F., Ramos, E.S.: Novel potential inhibitors for adenylylsulfate reductase to control souring of water in oil industries. J. Biomol. Struct. Dyn. 32, 1780–1792 (2014)

    Article  Google Scholar 

  9. Santos, S.E., Gritta, D.H.S., Almeida, J.S.: Analysis of interactions between potent inhibitors of ATP sulfurylase via molecular dynamics. Mol. Simul. 42, 605–610 (2015)

    Article  Google Scholar 

  10. Fraternali, F., Van Gunsteren, W.F.: An efficient mean solvation force model for use in molecular dynamics simulations of proteins in aqueous solution. J. Mol. Biol. 256, 939–948 (1996)

    Article  Google Scholar 

  11. Soares, C.M., Teixeira, V.H., Baptista, A.M.: Protein structure and dynamics in nonaqueous solvents: insights from molecular dynamics simulation studies. Biophys. J. 84, 1628–1641 (2003)

    Article  ADS  Google Scholar 

  12. Friedman, R.: Ions and the protein surface revisited: extensive molecular dynamics simulations and analysis of protein structures in alkali-chloride solutions. J. Phys. Chem. B 115, 9213–9223 (2011)

    Article  Google Scholar 

  13. Ahlstrom, P., Teleman, O., Jonsson, B., Forsén, S.: Molecular dynamics simulation of parvalbumin in aqueous solution. J. Am. Chem. Soc. 109, 1541–1551 (1987)

    Article  Google Scholar 

  14. Avvakumov, G.V., Muller, Y.A., Hammond, G.L.: Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site. J. Biol. Chem. 275, 25920–25925 (2000)

    Article  Google Scholar 

  15. Boström, M., Williams, D.R., Ninham, B.W.: Specific ion effects: why the properties of lysozyme in salt solutions follow a Hofmeister series. Biophys. J. 85, 686–694 (2003)

    Article  Google Scholar 

  16. Stanaway, S.E.R.S., Gill, G.V.: Protein glycosylation in diabetes mellitus: biochemical and clinical considerations. Pract. Diab. Int. 17, 21–25 (2000)

    Article  Google Scholar 

  17. Neelofar, K., Arif, Z., Alam, K., Ahmad, J.: Hyperglycemia-induced structural and functional changes in human serum albumin of diabetic patients: a physico-chemical study. Mol. BioSyst. 12, 2481–2489 (2016)

    Article  Google Scholar 

  18. Roy, A., Sil, R., Chakraborti, A.S.: Non-enzymatic glycation induces structural modifications of myoglobin. Mol. Cell. Biochem. 338, 105–114 (2010)

    Article  Google Scholar 

  19. Anderson, D.C.: Sex-hormone-binding globulin. Clin. Endocrinol. 3, 69–96 (1974)

    Article  Google Scholar 

  20. Damassa, D.A., Cates, J.M.: Sex hormone-binding globulin and male sexual development. Neurosci. Biobehav. Rev. 19, 165–175 (1995)

    Article  Google Scholar 

  21. Selby, C.: Sex hormone binding globulin: origin, function and clinical significance. Ann. Clin. Biochem. 27, 532–541 (1990)

    Article  Google Scholar 

  22. Grishkovskaya, I., Avvakumov, G.V., Sklenar, G., Dales, D., Hammon, G.L., Muller, Y.A.: Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 19, 504–512 (2000)

    Article  Google Scholar 

  23. Ding, E.L., Song, Y., Manson, J.E., Hunter, D.J., Lee, C.C., Rifai, N., Buring, J.E., Gaziano, J.M., Liu, S.: Sex hormone–binding globulin and risk of type 2 diabetes in women and men. N. Engl. J. Med. 361, 1152–1163 (2009)

    Article  Google Scholar 

  24. Hautanen, A.: Synthesis and regulation of sex hormone-binding globulin in obesity. Int. J. Obes. Relat. Metab. Disord. Suppl. 2, S64–S70 (2000)

    Article  Google Scholar 

  25. Wang, Y.M., Bayliss, D.A., Millhorn, D.E., Petrusz, P., Joseph, D.R.: The androgen-binding protein gene is expressed in male and female rat brain. Endocrinology 127, 3124–3130 (1990)

    Article  Google Scholar 

  26. Gnanasekar, M., Suleman, F.G., Ramaswamy, K., Caldwell, J.D.: Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening. Int. J. Mol. Med. 24, 421–426 (2009)

    Article  Google Scholar 

  27. Simpson, E., Santen, R.J.: Celebrating 75 years of oestradiol. J. Mol. Endocrinol. 55, T1–T20 (2015)

    Article  ADS  Google Scholar 

  28. Södergård, R., Bäckström, T., Shanbhag, V., Carstensen, H.: Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J. Steroid Biochem. 16, 801–810 (1982)

    Article  Google Scholar 

  29. Anstead, G.M., Carlson, K.E., Katzenellenbogen, J.A.: The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 62, 268–303 (1997)

    Article  Google Scholar 

  30. Toran-Allerand, C.D., Tinnikov, A.A., Singh, J.R., Nethrapalli, I.S.: 17 alpha-estradiol: a brain-active estrogen? Endocrinology 146, 3843–3850 (2005)

    Article  Google Scholar 

  31. Danzo, B.J., Eller, B.C.: The presence of a cytoplasmic estrogen receptor in sexually mature rabbit epididymides: comparison with the estrogen receptor in immature rabbit epididymal cytosol. Endocrinology 105, 1128–1134 (1979)

    Article  Google Scholar 

  32. Cornil, C.A., Ball, G.F., Balthazart, J.: Functional significance of the rapid regulation of brain estrogen action: where do the estrogens come from? Brain Res. 1126, 2–26 (2006)

    Article  Google Scholar 

  33. Hess, R.A., Carnes, K.: The role of estrogen in testis and the male reproductive tract: a review and species comparison. Anim. Reprod. 1, 5–30 (2004)

    Google Scholar 

  34. Gruber, C.J., Tschugguel, W., Schneeberger, C., Huber, J.C.: Productions and actions of estrogens. N. Engl. J. Med. 346, 340–352 (2002)

    Article  Google Scholar 

  35. Rupprecht, R., Holsboer, F.: Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 22, 410–416 (1999)

    Article  Google Scholar 

  36. Falkenstein, E., Tillmann, H.-C., Christ, M., Feuring, M., Wehling, M.: Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol. Rev. 52, 513–555 (2000)

    Google Scholar 

  37. O'Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T., Hutchison, G.R.: Open Babel: an open chemical toolbox. J. Cheminform. 3, 1–14 (2011)

    Article  Google Scholar 

  38. Alizadeh-Rahrovi, J., Shayesteh, A., Ebrahim-Habibi, A.: Structural stability of myoglobin and glycomyoglobin: a comparative molecular dynamics simulation study. J. Biol. Phys. 41, 349–366 (2015)

    Article  Google Scholar 

  39. Tautermann, C.S., Seeliger, D., Kriegl, J.M.: What can we learn from molecular dynamics simulations for GPCR drug design? Comput. Struct. Biotechnol. J. 13, 111–121 (2015)

    Article  Google Scholar 

  40. Gajula, M.P., Kumar, A., Ijaq, J.: Protocol for molecular dynamics simulations of proteins. Bio-protocol. 6, e205 (2016)

    Article  Google Scholar 

  41. Halgren, T.A.: MMFF VI. MMFF94s option for energy minimization studies. J. Comput. Chem. 20, 720–729 (1999)

    Article  Google Scholar 

  42. DeLano, W.L.: The PyMOL Molecular Graphics System (Version 1.8). DeLano Scientific LLC. Accessed in, San Carlos (2016)

    Google Scholar 

  43. Trott, O., Olson, O.J.: AutoDock Vina: improving speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 31, 455–461 (2010)

    Google Scholar 

  44. Abraham, M.J., van der Spoel, D., Lindahl, E., Hess, B.: GROMACS development team, GROMACS. www.gromacs.org, User manual version 5.0.2 (2014)

  45. Zoete, V., Cuendet, M.A., Grosdidier, A., Michielin, O.: SwissParam, a fast force field generation tool for small organic molecules. J. Comput. Chem. 32, 2359–2368 (2011)

    Article  Google Scholar 

  46. Ryckaert, J.P., Ciccotti, G., Berendsen, H.J.C.: Numeral integration of the Cartesian equation of motion of a system with constrains; molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977)

    Article  ADS  Google Scholar 

  47. Miyamoto, S., Kollman, P.A.: SETTLE: an analytical version of the shake an RATTLE algorithms for molecular simulation. J. Comput. Chem. 13, 952–962 (1992)

    Article  Google Scholar 

  48. Darden, T., York, D., Pedersen, L.J.: Particle mesh Ewald: an N·log (N) method for Ewald sums in large systems. J. Chem. Phys. 103, 8577–8593 (1993)

    Google Scholar 

  49. Salvalaglio, M., Perego, C., Giberti, F., Mazzotti, M., Parrinello, M.: Molecular-dynamics simulations of urea nucleation from aqueous solution. Proc. Natl. Acad. Sci. U.S.A. 112, E6–E14 (2015)

    Article  ADS  Google Scholar 

  50. Anwar, M.A., Choi, S.: Structure-activity relationship in TLR4 mutations: atomistic molecular dynamics simulations and residue interaction network analysis. Sci. Rep. 7, 43807 (2017)

    Article  ADS  Google Scholar 

  51. Shanbhag, V.P., Södergård, R.: The temperature dependence of the binding of 5α- dihydrotestosterone, testosterone and estradiol to the sex hormone globulin (SHBG) of human plasma. J. Steroid Biochem. 24, 549–555 (1986)

    Article  Google Scholar 

  52. Hansson, T., Marelius, J., Åqvist, J.: Ligand binding affinity prediction by linear interaction energy methods. J. Comput. Aided Mol. Des. 12, 27–35 (1998)

    Article  ADS  Google Scholar 

  53. Zwanzig, R.W.: High-temperature equation of state by a perturbation method. I. Nonpolar gases. J. Chem. Phys. 22, l1420–l1426 (1954)

    Article  ADS  Google Scholar 

  54. Åqvist, J., Marelius, J.: The linear interaction energy method for predicting ligand binding free energies. Comb. Chem. High Throughput Screen. 4, 613–626 (2001)

    Article  Google Scholar 

  55. von Hippel, P.H., Schleich, T.: In: Timasheff, S.N., Fasman, G.D. (eds.) Structure and Stability of Biological Macromolecules, pp. 416–574. Dekker, New York (1969)

    Google Scholar 

  56. Carter, J.E.A., Sluss, P.M.: Estradiol solubility in aqueous systems: effect of ionic concentrations, pH, and organic solvents. Journal of Hormones 2013, 1–4 (2013)

    Article  Google Scholar 

  57. Ben-Naim, A.: The rise and fall of the hydrophobic effect in protein folding and protein-protein association and molecular recognition. Open J. Biophys. 1, 1–7 (2011)

    Article  ADS  Google Scholar 

  58. Kim, J.S., Wu, Z., Morrow, A.R., Yethiraj, A., Yethiraj, A.: Self-diffusion and viscosity in electrolyte solutions. J. Phys. Chem. B 116, 12007–12013 (2012)

    Article  Google Scholar 

  59. Ma, L., Cui, Q.: Temperature dependence of salt-protein association is sequence specific. Biochemistry 45, 14466–14472 (2006)

    Article  Google Scholar 

  60. Ding, Y., Hassanali, A.A., Parrinello, M.: Anomalous water diffusion in salt solutions. Proc. Natl. Acad. Sci. U.S.A. 111, 3310–3315 (2014)

    Article  ADS  Google Scholar 

  61. Rajamani, S., Ghosh, T., Garde, S.: Size dependent ion hydration, its asymmetry, and convergence to macroscopic behaviour. J. Chem. Phys. 120, 4457–4466 (2004)

    Article  ADS  Google Scholar 

  62. Katzenellenbogen, J.A., Heiman, D.F., Carlson, K.E., Lloyd, J.E.: In vivo and in vitro steroid receptor assays in the design of estrogen pharmaceuticals. In: Eckelman, W.C. (ed.) Receptor-Binding Radiotracers, Vol. I, pp. 93–126. CRC, Florida (1982)

    Google Scholar 

  63. Chandra, A.: Static dielectric constant of aqueous electrolyte solutions: is there any dynamic contribution? J. Chem. Phys. 113, 903 (2000)

    Article  ADS  Google Scholar 

  64. Li, Y., Girard, M., Shen, M., Millan, J.A., Cruz, M.O.: Strong attractions and repulsions mediated by monovalent salts. Proc. Natl. Acad. Sci. 114, 11838–11843 (2017)

    Article  Google Scholar 

  65. Zasetsky, A.Y., Svishchev, I.M.: Dielectric response of concentrated NaCl aqueous solutions: molecular dynamics simulations. J. Chem. Phys. 115, 1448 (2001)

    Article  ADS  Google Scholar 

  66. Anderson, J., Ullo, J., Yip, S.: Molecular dynamics simulation of the concentration-dependent dielectric constants of aqueous NaCl solutions. Chem. Phys. Lett. 152, 447–452 (1988)

    Article  ADS  Google Scholar 

  67. Payne, V.A., Xu, J.-H., Forsyth, M., Ratner, M.A., Duward, F.S., Leeuw, S.W.: Clustering in molecular dynamics simulations of sodium iodide solutions. Electrochim. Acta 40, 2087–2091 (1995)

    Article  Google Scholar 

  68. Payne, V.A., Xu, J.-H., Forsyth, M., Ratner, M.A., Duward, F.S., Leeuw, S.W.: Molecular dynamics simulations of ion clustering and conductivity in NaI/ether solutions. I. Effect of ion charge. J. Chem. Phys. 103, 8734–8745 (1995)

    Article  ADS  Google Scholar 

  69. Payne, V.A., Xu, J.-H., Forsyth, M., Ratner, M.A., Duward, F.S., Leeuw, S.W.: Molecular dynamics simulations of ion clustering and conductivity in NaI/ether solutions. II. Effect of ion concentration. J. Chem. Phys. 103, 8746–8755 (1995)

    Article  ADS  Google Scholar 

  70. Brodholt, J.P.: Molecular dynamics simulations of aqueous NaCl at high pressures and temperatures. Chem. Geol. 151, 11–19 (1998)

    Article  ADS  Google Scholar 

  71. Friedman, R., Nachliel, E., Gutman, M.: Protein surface dynamics: interaction with water and small solutes. J. Biol. Phys. 31, 433–452 (2005)

    Article  Google Scholar 

  72. Pfeiffer, S., Fushman, D., Cowburn, D.: Impact of Cl− and Na+ ions on simulated structure and dynamics of βARK1 PH domain. Proteins 35, 206–217 (1999)

    Article  Google Scholar 

  73. Mokhdomi, T.A., Bukhari, S., Naveed, A.C., Amin, A., Wafai, A.H., Wani, S.H., Chowdri, N.A., Qadri, R.A.: A novel kinase mutation in VEGFR-1 predisposes its αC-helix/activation loop towards allosteric activation: atomic insights from protein simulation. Eur. J. Hum. Genet. 24, 1287–1293 (2016)

    Article  Google Scholar 

  74. Ul-Haq, Z., Usmani, S., Iqbal, S., Zia, S.R.: In silico based investigation of dynamic variations in neprilysin (NEP and NEP2) proteins for extracting the point of specificity. Mol. BioSyst. 12, 1024–1036 (2016)

    Article  Google Scholar 

  75. Ramharack, P., Oguntade, S., Soliman, M.E.S.: Delving into Zika virus structural dynamics—a closer look at NS3 helicase loop flexibility and its role in drug discovery. RSC Adv. 7, 22133–22144 (2017)

    Article  Google Scholar 

  76. Aykut, A.O., Atilgan, A.R., Atilgan, C.: Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin. PLoS Comput. Biol. 12, e1003366 (2013)

    Article  Google Scholar 

  77. Gao, N., Liang, T., Yuan, Y., Xiao, X., Zhao, Y., Guo, Y., Li, M., Pu, X.: Exploring the mechanism of F282L mutation-caused constitutive activity of GPCR by a computational study. Phys. Chem. Chem. Phys. 18, 29412–29422 (2016)

    Article  Google Scholar 

  78. Bye, J.W., Falconer, R.J.: Thermal stability of lysozyme as a function of ion concentration: a reappraisal of the relationship between the Hofmeister series and protein stability. Protein Sci. 22, 1563–1570 (2013)

    Article  Google Scholar 

  79. Chen, C., Li, W.Z., Song, Y.C., Weng, L.D., Zhang, N.: Formation of water and glucose clusters by hydrogen bonds in glucose aqueous solutions. Comput. Theor. Chem. 984, 85–92 (2012)

    Article  Google Scholar 

  80. Bulavin, L.A., Vergun, L.Y., Zabashta, Y.F., Teliman, E.O.: Large scaled clusters in aqueous glucose solutions. Colloid J. 77, 261–266 (2015)

    Article  Google Scholar 

  81. Perry, J.R., Weedon, M.N., Langenberg, C., et al.: Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum. Mol. Genet. 19, 535–544 (2010)

    Article  Google Scholar 

  82. Imamura, K., Ogawa, T., Sakiyama, T., Nakanishi, K.: Effects of types of sugar on the stabilization of protein in the dried state. J. Pharm. Sci. 92, 266–274 (2003)

    Article  Google Scholar 

  83. Arakawa, T., Timasheff, S.N.: Stabilization of protein structure by sugars. Biochemistry 21, 6536–6544 (1982)

    Article  Google Scholar 

  84. Wong, Y.-H., Tayyab, S.: Protein stabilizing potential of simulated honey sugar cocktail under various denaturation conditions. Process Biochem. 47, 1933–1943 (2012)

    Article  Google Scholar 

  85. Ohan, M.P., Dunn, M.G.: Glucose stabilizes collagen sterilized with gamma irradiation. J. Biomed. Mater. Res. A 67, 1188–1195 (2003)

    Article  Google Scholar 

  86. Lins, R.D., Pereira, C.S., Hünenberger, P.H.: Trehalose–protein interaction in aqueous solution. Proteins 55, 177–186 (2004)

    Article  Google Scholar 

  87. Mittal, S., Chowhan, R.K., Rajendrakumar, L.: Macromolecular crowding: macromolecules friend or foe. Biochim. Biophys. Acta 1850, 1822–1831 (2015)

    Article  Google Scholar 

  88. Waseda, Y., Ohtani, M.: Structure and effective interionic potential of liquid palladium, platinum and zirconium. Z. Physik B 21, 229–234 (1975)

    Article  ADS  Google Scholar 

  89. Lyubartsev, A.P., Laaksonen, A.: Concentration effects in aqueous NaCl solutions. A molecular dynamics simulation. J. Phys. Chem. 100, 16410–16418 (1996)

    Article  Google Scholar 

  90. Filipponi, A., DiCicco, A., Aquilanti, G., Minicucci, M., De Panfilis, S., Rybicki, J.: Short-range structure of liquid palladium and rhodium at very high temperatures. J. Non-Cryst. Solids 250-252, 172–176 (1999)

    Article  ADS  Google Scholar 

  91. Balbuena, P.B., Johnston, K.P., Rossky, P.J.: Molecular dynamics simulation of electrolyte solutions in ambient and supercritical water. 1. Ion solvation. J. Phys. Chem. 100, 2706–2715 (1996)

    Article  Google Scholar 

  92. Bocchinfuso, W.P., Ma, K.L., Lee, W.M., Warmels-Rodenhiser, S., Hammond, G.L.: Selective removal of glycosylation sites from sex hormone-binding globulin by site-directed mutagenesis. Endocrinology 131, 2331–2336 (1992)

    Article  Google Scholar 

Download references

Acknowledgements

We thank Prof. Márcio R. Maia and Cintia Garcia for reading the manuscript. We are also in debt to Prof. D.O.C. Santos for her valuable help during the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Instituto de Humanidades, Artes e Ciências, Universidade Federal do Sul da Bahia, Itabuna, Bahia, 45613-204, Brazil

    A. J. da Silva

  2. Instituto de Física, Universidade Federal da Bahia, Campus Universitário de Ondina, Salvador, Bahia, 40210-340, Brazil

    E. S. dos Santos

Authors
  1. A. J. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. S. dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. J. da Silva.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Electronic supplementary material

ESM 1

(PDF 241 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, A.J., dos Santos, E.S. Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation. J Biol Phys 44, 539–556 (2018). https://doi.org/10.1007/s10867-018-9505-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10867-018-9505-8

Keywords

Search

Navigation