CSTA  Vol.8 No.2 , May 2019
Docking of Human Heat Shock Protein 90 with Selenoderivatives of Geldanamycin
Abstract: The interference of human heat shock protein 90 (HSP90) in many signalling networks associated with cancer progression makes it an important drug target. In the present work, we investigated the binding ability of 9 selenoderivatives of geldanamycin (GMDSe) at the N-terminal domain of HSP90 derived from Protein Data Bank (PDB code: 1YET) based on ligand-protein docking. All selenoderivatives interacted positively with HSP90, yet the binding strength decreased when replacing monovalent oxygen in position 1 (GMDSe1) or 9 (GMDSe9). Hydrogen-bonding and lipophilic interactions between selenoderivatives and amino acid residues in the inhibitor site of HSP90 were thermodynamically the main forces driving the binding stability. Molecular electrostatic potential surfaces of the selenoderivatives showed marked non polar areas, which were probably involved in the lipophilic interactions with the hydrophobic residues of amino acids. Interestingly, the amino acid residues forming the hydrogen bonds with GMD were also involved in the hydrogen-bonding interactions with the selenoderivatives. Moreover, HSP90 interacted with the GMDSe6 and GMDSe7 selenoderivatives stronger than with GMD, while maintaining lipophilic interactions and hydrogen bonds with amino acid residues like Asp93, which are catalytically crucial for therapeutic properties of HSP90 inhibitors. This finding should guide further studies of pharmacophore properties of GMD selenoderivatives in order to explore their therapeutic properties. It is noteworthy that selenium has been suggested to reduce the risk of various types of cancers.
Cite this paper: Kilembe, J. , Lundemba, A. , Bibelayi, D. , Ndefi, G. , Pradon, J. and Yav, Z. (2019) Docking of Human Heat Shock Protein 90 with Selenoderivatives of Geldanamycin. Crystal Structure Theory and Applications, 8, 13-27. doi: 10.4236/csta.2019.82002.

[1]   Chatterjee, S., Bhattacharya, S., Socinski, M.A. and Burns, T.F. (2016) HSP90 Inhibitors in Lung Cancer: Promise Still Unfulfilled. Clinical Advances in Hematology & Oncology, 14, 346-356.

[2]   Ghaemmaghami, S., Huh, W.K., Bower, K. and Howson, R.W. (2003) Global Analysis of Protein Expression in Yeast. Nature, 425, 737-741.

[3]   Whitesell, L. and Lindquist, S.L. (2005) HSP90 and the Chaperoning. Nature, 5, 761-772.

[4]   Abbasi, M., Henrry, S.-A. and Amanlou, M. (2017) Prediction of New HSP90 Inhibitors Based on 3,4-Isoxazolediamide Scaffold Using QSAR Study, Molecular Docking and Molecular Dynamic Simulation. DARU Journal of Pharmaceutical Sciences, 25, 17.

[5]   Sawai, A., Chandarlapaty, S., Greulich, H., Gonen, M., Yee, Q., Arteaga, C.L. and Solit, D.B. (2008) Inhibition of HSP90 Down-Regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel. Cancer Research, 68, 589-597.

[6]   Goetz, M.P., Toft, D.O., Ames, M.M. and Erlichman, C. (2003) The HSP90 Chaperone Complex as a Novel Target for Cancer Therapy. Annals of Oncology, 90, 1169-1176.

[7]   Hyun, S., Woo, J.K., Yazici, Y.D., Niamh, M.O., Andrew, J.S., Trevor, T.P., Clive, W., Zisterer, D.M., Lloyd, D.G. and Meegan, M.J. (2011) Lead Identification of β-Lactam and Related Imine Inhibitors of the Molecular Chaperone Heat Shock Protein 90. Bioorganic & Medicinal Chemistry, 19, 6055-6068.

[8]   Baby, S.T., Sharma, S., Enaganti, S. and Cherian, P.R. (2016) Molecular Docking and Pharmacophore Studies of Heterocyclic Compounds as Heat Shock Protein 90 (HSP90) Inhibitors. Bioinformation, 12, 149-155.

[9]   Ahmad, M.S., Yasser, M.M., Sholkamy, E.N., Ali, A.M. and Mehanni, M.M. (2015) Anticancer Activity of Biostabilized Selenium Nanorods Synthesized by Streptomyces Bikiniensis Strain Ess_amA-1. International Journal of Nanomedicine, 10, 3389-3401.

[10]   Frisch, M.J., Trucks, G.W., Schlegel, H.B., et al. (2009) Gaussian 09 Revision C 01 Gaussian 09 Revis B01. Gaussian Inc., Wallingford.

[11]   Nissink, J.W.M., Murray, C., Hartshorn, M., Verdonk, M.L., Cole, J.C. and Taylor, R. (2002) New Test Set for Validating Predictions of Protein-Ligand Interaction. Proteins, 49, 457-471.

[12]   Eldridge, M.D., Murray, C.W., Auton, T.R., Paolini, G.V. and Mee, R.P. (1997) Empirical Scoring Functions?: I. The Development of a Fast Empirical Scoring Function to Estimate the Binding Affinity of Ligands in Receptor Complexes. Journal of Computer-Aided Molecular Design, 11, 425-445.

[13]   Lauria, A., Ippolito, M. and Almerico, A.M. (2009) Inside the HSP90 Inhibitors Bindingmode through Induced Fit Docking. Journal of Molecular Graphics and Modelling, 27, 712-722.

[14]   Cole, J.C., Murray, C.W., Nissink, J.W.M. and Taylor, R.D. (2005) Comparing Protein-Ligand Docking Programs Is Difficult. Proteins, 60, 325-332.

[15]   Gabb, J. and Jackson, R.M. (1997) Modelling Protein Docking Using Shape Complementarity, Electrostatics and Biochemical Information. Journal of Molecular Biology, 272, 106-120.

[16]   Zaheer, U.H., Sobia, A.H, Reaz, U. and Jeffry, D. (2010) Benchmarking Docking and Scoring Protocol for the Identification of Potential Acetyl Cholinesterase Inhibitors. Journal of Molecular Graphics and Modelling, 28, 870-882.

[17]   Michael, L. and Christopher, E. (2010). Comparison of Current Docking Tools for the Simulation of Inhibitor Binding by the Transmembrane Domain of the Sarco/Endoplasmic Reticulum Calcium ATPase. Biophysical Chemistry, 150, 88-97.

[18]   Hioual, K.S., Chikhi, A., Bensegueni, A. and Merzoug, A. (2012) Comparative Data on Docking Algorithms: Keeping the Update in the Field Knowledge. The International Journal of Accounting Information Systems, 2, 2249-0868.

[19]   Politzer, P., Murray, J.S. and Clark, T. (2013) Halogen Bonding and Other Sigma-Hole Interactions: A Perspective. Physical Chemistry Chemical Physics, 15, 1117-11189.

[20]   Metrangolo, P., Neukirch, H., Pilati, T. and Resnati, G. (2005) Halogen Bonding Based Recognition Processes: A World Parallel to Hydrogen Bonding. Accounts of Chemical Research, 38, 386-395.

[21]   Bibelayi, D., Lundemba, A.S., Allen, F.H., Galek, P.T.A., Pradon, J., Reilly, A.M. and Yav, Z.G. (2016) Hydrogen Bonding at C = Se Acceptors in Selenoureas, Selenoamides and Selones. Acta Crystallographica, B72, 317-325.

[22]   Abasi, M., Sadeghi-Aliabadi, H. and Amanlou, M. (2018) 3D-QSAR, Molecular Docking, and Molecular Dynamic Simulations for Prediction of New HSP90 Inhibitors Based on Isoxazole Scaffold. Journal of Biomolecular Structure and Dynamics, 36, 1463-1478.

[23]   Sepehri, B. and Ghavani, R. (2019). Towards the In-Silico Design of New HSP90 Inhibitors: Molecular Docking and 3D-QSAR CoMFA Studies of Tetrahydropyrido [4, 3-d] Pyrimidine Derivatives as HSP90 Inhibitors. Journal of Medicinal Chemistry, 14, 439-450.

[24]   Rowland, R.S. and Taylor, R. (1996) Intermolecular Nonbonded Contact Distances in Organic Crystal Structures: Comparison with Distances Expected from van der Waals Radii. The Journal of Physical Chemistry, 100, 7384-7391.

[25]   Bondi, A. (1964) Van der Waals Volumes and Radii. The Journal of Physical Chemistry, 68, 441-451.

[26]   Wood, P.A., Pidcock, E. and Allen, F.H. (2008) Interaction Geometries and Energies of Hydrogen Bonds to C = O and C = S Acceptors: A Comparative Study. Acta Crystallographica, B64, 491-496.