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Computational analyses on delineating specificity of 2-hydroxy-3,5-dinitrobenzamide, a BH3-mimetic, towards anti-apoptotic proteins
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)
Journal: Bangladesh Journal of Pharmacology
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• Bangladesh Pharmacological Society
• ISSN: 1991-0088
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.
Dakshinamurthy Sivakumar, Natarajan Hari, Thirunavukkarasu Sivaraman (2014). "Computational analyses on delineating specificity of 2-hydroxy-3,5-dinitrobenzamide, a BH3-mimetic, towards anti-apoptotic proteins". Bangladesh Journal of Pharmacology.