Abstract
Human serum albumin (HSA) is the most abundant protein in the blood serum. It binds several ligands and has an especially strong affinity for heme, hence becoming a natural candidate for oxygen transport. In order to analyze the interaction of HSA-heme, molecular dynamics simulations of HSA with bound heme were performed. Based on the results of X-ray diffraction, the binding site of the heme, localized in subdomain IB, was considered. We analyzed the fluctuations and their correlations along trajectories to detect collective motions. The role of H bonds and salt bridges in the stabilization of heme in its pocket was also investigated. Complementarily, the localization of water molecules in the hydrophobic pocket and the interaction with heme were discussed.
Similar content being viewed by others
Notes
The overlap between the subspaces spanned by orthonormal eigenvectors \(\{{\bf u}_{1}, \ldots, {\bf u}_{N}\}\; \hbox{ and }\; \{{\bf v}_{1}, \ldots, {\bf v}_{N}\}\) is defined as \({{\mathcal O} = \frac{1}{N} \sum\nolimits_{i,j=1}^{N} ({\bf u}_{i} .{\bf v}_{j})^{2}}\).
Porcupine plots were obtained using the Dynatrj tool of the Dynamite web server (http://s12-ap550.bioch.ox.ac.uk:8078/dynamite_html/index.html).
References
Arnold GE, Ornstein RL (1997) Molecular dynamics study of time-correlated protein motion and molecular flexibility: cytochrome P450BM-3. Biophys J 73:1147–1159
Ascenzi P, Bolli A, di Massi A, Tundo GR, Fanali G, Colleta M, Fasano M (2011) Isoniazid and rifampicin inhibit allosterically heme binding to albumin and peroxynitrite isomerization by heme-albumin. Biol Inorg Chem 16:97–108
Barrett CP, Hall BA, Noble MEM (2004) Dynamite: a simple way to gain insight into protein motions. Acta Cryst D 60:2280–2287
Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) In: Pullman B (ed) Intermolecular forces. D. Reidel, Dordrecht
Berendsen HJC, Postma JPM, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242. http://www.pdb.org
Bradley MJ, Chivers PT, Baker NA (2008)Molecular dynamics simulation of the Escherichia coli NikR protein: equilibrium conformational fluctuations. J Mol Biol 378:1155–1173
Connolly ML (1983) Solvent-accessible surfaces of proteins and nucleic acids. Science 221:709–713
Cuya TR, da Rocha Pita S, Louro SRW, Pascutti PG (2008) Computational study of the solvation of protoporphyrin IX and its Fe2+ complex. Int J Quantum Chem 108:2603–2607
Cuya Guizado TR, Louro SRW, Pascutti PG, Anteneodo C (2010) Solvation of anionic water-soluble porphyrins: a computational study. Int J Quantum Chem 110:2094–2100
Cuya Guizado TR, Louro SRW, Anteneodo CJ (2011) Hydration of hydrophobic biological porphyrins. J Chem Phys 134:(055103)1–9
de Groot BL, van Aalten DMF, Amadei A, Berendsen HJC (1996) The consistency of large concerted motions in proteins in molecular dynamics simulations. Biophys J 71:1707–1713
Dockal M, Carter DC, Ruker F (1999) The three recombinant domains of human serum albumin. J Biol Chem 274:29303–29310
Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593
Fujiwara S, Amisaki T (2006) Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids. Proteins 64:730–739
Guex N, Peitsch MC (1997) Swiss-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723
Hayward S, Lee RA (2002) Improvements in the analysis of domain motions in proteins from conformational change: DynDom version 1.50. J Mol Graph Model 21:181–183. http://fizz.cmp.uea.ac.uk/dyndom/
Hess B (2000) Similarities between principal components of protein dynamics and random diffusion. Phys Rev E 62:8438–8448
Horta BAC, Cirino JJV, de Alencastro RB (2007) Dynamical behavior of the vascular endothelial growth factor: biological implications. Proteins 67:517–525
Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38
Kiselev MA, Gryzunov YA, Dobretsov GE, Komarova MN (2001) Size of a human serum albumin molecule in solution. Biofizika 2001(46):423–427
Komatsu T, Ohmichi N, Zunszain PA, Curry E, Tsuchida E (2004) Dioxygenation of human serum albumin having a prosthetic heme group in a tailor-made heme pocket. J Am Chem Soc 126:14304–14305
Komatsu T, Nakagawa A, Zunszain PA, Curry S, Tsuchida E (2007) Genetic engineering of the heme pocket in human serum albumin: modulation of O2 binding of iron protoporphyrin IX by variation of distal amino acids. J Am Chem Soc 129(36):11286–11295
Lange OF, Grubmuller H (2006) Generalized correlation for biomolecular dynamics. Proteins 62:1053–1061
Lee AL, Wand AJ (2001) Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411:501–504
Nelson DL, Cox MM (2000) Principles of biochemistry, 4th edn, p 79
Nocedal J (1980) Updating quasi-Newton matrices with limited storage. Math Comput 35:773–782
Scheer A, Cotecchia S (1997) Constitutivelt active G protein-coupled receptors: potential mechanisms of receptor activation. J Recept Signal Transduct Res 17:57–73
Software developed at the Laboratory of Modeling and Molecular Dynamics of the Biophysics Institute Carlos Chagas Filho - Universidade Federal de Rio de Janeiro
Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K (1999) Crystal structure of human serum albumin at 2.5 resolution. Protein Eng 12:439–446
van der Spoel D et al (2002) Gromacs user manual. Nijenborgh, Groningen. Available at http://www.gromacs.org
Wang R, Komatsu T, Nakagawa A, Tsuchida E (2005) Human serum albumin bearing covalently attached iron(ii) porphyrins as O2-coordination sites. Bioconj Chem 16:23–26
Wardell M, Wang Z, Ho JX, Justin R, Ruker F, Ruble J, Carter C (2002) The atomic structure of human serum albumin at 1.9. Biochem Biophys Res Commun 291:813–819
Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S (2003) Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol 3:6. Available at http://www.biomedcentral.com/1472-6807/3/6
Acknowledgments
We acknowledge the Brazilian agencies Faperj (Foundation for Research Support, State of Rio de Janeiro) and CNPq (National Council for Scientific and Technological Development) for partial financial support. We are grateful to Pedro G. Pascutti for his useful advice about molecular modeling. We also acknowledge the developers of the free Linux software.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guizado, T.R.C., Louro, S.R.W. & Anteneodo, C. Dynamics of heme complexed with human serum albumin: a theoretical approach. Eur Biophys J 41, 1033–1042 (2012). https://doi.org/10.1007/s00249-012-0860-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-012-0860-2