Docking of Human Heat Shock Protein 90 with Selenoderivatives of Geldanamycin - Crystal Structure Theory and Applications

CSTA > Vol.8 No.2, May 2019

Crystal Structure Theory and Applications

Volume 8, Issue 2 (May 2019)

ISSN Print: 2169-2491 ISSN Online: 2169-2505

Google-based Impact Factor: 0.43 Citations

Docking of Human Heat Shock Protein 90 with Selenoderivatives of Geldanamycin ()

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DOI: 10.4236/csta.2019.82002 564 Downloads 1,467 Views Citations

Author(s)

Jason T. Kilembe¹, Albert S. Lundemba¹, Dikima D. Bibelayi¹, Glodi M. Ndefi¹, Juliette Pradon², Zéphyrin G. Yav^1*

Affiliation(s)

¹Department of Chemistry, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
²The Cambridge Crystallographic Data Centre, Cambridge, UK.

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.

KEYWORDS

1YET, Geldanamycin, Selenoderivatives, Cambridge Structural Database, Binding Energy, Molecular Electrostatic Potential (MEP)

Share and Cite:

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.

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