Design and computational analysis of a novel Azurin-BR2 chimeric protein against breast cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Bioinformatics

Background:

• Cancer remains a leading cause of death globally, with current treatments like chemotherapy and surgery having limitations.
• Drug resistance and damage to normal cells necessitate the development of novel cancer treatment strategies.
• Microbial products, such as Pseudomonas aeruginosa Azurins, show promise for cancer therapy due to their selective effects.

Purpose of the Study:

• To computationally evaluate the anticancer potential of a novel Azurin-BR2 chimeric protein.
• To enhance the cytotoxic effect and targeted delivery of Azurin for cancer treatment.
• To investigate the binding affinity of the Azurin-BR2 fusion protein with the cancer suppressor protein p53.

Main Methods:

• In silico analysis was employed to predict the secondary and tertiary structures of the chimeric protein.
• Physicochemical properties, quality indices (ERRAT2), and validation (Ramachandran plot) were computationally assessed.
• The HDOCK bioinformatics tool was used for molecular docking of the Azurin-BR2 protein with p53.

Main Results:

• The Azurin-BR2 chimeric protein was characterized computationally, showing a basic nature and a molecular weight of 16.8 kDa.
• Quality indices ranged from 81% to 84.6%, with validated residues in favored regions.
• Docking analysis revealed a high binding affinity between the Azurin-BR2 fusion protein and p53.

Conclusions:

• The Azurin-BR2 fusion protein exhibits significant potential for inducing apoptosis in cancerous cells.
• This chimeric protein demonstrates promise for developing advanced tumor-targeting cancer therapies.
• Computational evaluation supports the therapeutic utility of Azurin-BR2 in cancer treatment.