Computational analyses on delineating specificity of 2-hydroxy-3,5-dinitrobenzamide, a BH3-mimetic, towards anti-apoptotic proteins

  • Dakshinamurthy Sivakumar Structural Biology Lab, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu
  • Natarajan Hari Department of Biotechnology, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu
  • Thirunavukkarasu Sivaraman Structural Biology Lab, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu
Keywords: Anti-apoptotic protein, Bcl-2 family, BH3-mimetic, 2-hydroxy-3, 5-dinitrobenzamide

Abstract

We have herein computationally examined binding affinities and specificity of 2-hydroxy-3,5-dinitrobenzamide (HDNB), a small chemical molecular BH3-mimetic identified by means of peptidodynmimetic method, on the BH3-binding grooves of six anti-apoptotic proteins (Bcl-2, Bcl-B, Bcl-W, Bcl-XL, Bfl-1 and Mcl-1) from human beings. The HDNB ligand was found to interact on the BH3-binding grooves of Bcl-2, Bcl-B, Bcl-XL, Bfl-1 and Mcl-1, whereas it did not act as BH3-mimetic to Bcl-W. Moreover, binding affinities of the HDNB towards the anti-apoptotic proteins were significantly different from each other. The differential binding affinities and specificity of the HDNB towards the anti-apoptotic proteins have been chiefly attributed to the differences in the chemical properties of BH3-binding grooves of the proteins. Implications of the study to design efficient de novo antagonists to the anti-apoptotic proteins using the HDNB as seed molecule have been discussed.

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Author Biography

Thirunavukkarasu Sivaraman, Structural Biology Lab, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu
Associate Professor

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Published
2014-07-23
How to Cite
Sivakumar, D., N. Hari, and T. Sivaraman. “Computational Analyses on Delineating Specificity of 2-Hydroxy-3,5-Dinitrobenzamide, a BH3-Mimetic, towards Anti-Apoptotic Proteins”. Bangladesh Journal of Pharmacology, Vol. 9, no. 3, July 2014, pp. 307-11, doi:10.3329/bjp.v9i3.18965.
Section
Research Articles