Computational analysis of bevacizumab binding with protein receptors for its potential anticancer activity

Abstract

Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. In this study, we investigated the binding free energy (ΔG) of bevacizumab, an anti-cancer therapy targeting angiogenesis through the inhibition of vascular endothelial growth factor (VEGF), with various proto-oncogenes including CDK4, EGFR, frizzled, IGFR, OmoMYC, and KIT. Our in-silico investigation revealed that hydrogen bonding is pivotal in inducing conformational changes within the DNA structure, impeding its replication and preventing cell death. Molecular docking results revealed the presence of crucial hydrogen bonds and supported the formation of stable bevacizumab complexes. The molecular docking scores for the tested complexes were CDK4 (Score = −7.2 kcal/mol), EGFR (Score = −8.5 kcal/mol), frizzled (Score = −6.9 kcal/mol), IGFR (Score = −7.8 kcal/mol), KIT (Score = −6.5 kcal/mol), and MYC (Score = −8.3 kcal/mol). The binding mode demonstrated vital hydrogen bonds correlated with the observed energy gap. Notably, the calculated binding free energies of the tested compounds are as follows: CDK4 (ΔG = 24275.195 ± 6411.293 kJ/mol), EGFR (ΔG = 363273.625 ± 8731.466 kJ/mol), frizzled (ΔG = 181751.990 ± 28438.515 kJ/mol), IGFR (ΔG = 162414.725 ± 10728.367 kJ/mol), KIT (ΔG = 40162.585 ± 4331.017 kJ/mol), and MYC (ΔG = 434783.463 ± 53989.676 kJ/mol). Furthermore, through extensive 100 ns MD simulations, we observed the formation of a stable bevacizumab complex structure. The simulations confirmed the stability of the bevacizumab complex with the proto-oncogenes. The results of this study highlight the potential of bevacizumab complex as a promising candidate for anticancer treatment. The identification of hydrogen bonding, along with the calculated binding free energies and molecular docking scores, provides valuable insights into the molecular interactions and stability of the bevacizumab complexes. These findings and the extensive MD simulations open new avenues for future research and development of bevacizumab as a targeted therapy for breast cancer and other related malignancies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Breast cancer
• bevacizumab
• molecular docking
• molecular dynamic simulation

Acknowledgement

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University Saudi Arabia for funding this work through Large Groups Project under grant number RGP2/360/44.

Disclosure statement

The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

Authors contributions

Nada Alsakhen, Enas S. Radwan, Imran Zafer: writing—original draft, investigation, and formal analysis; Enas S. Radwan, Husam Abed alfattah: editing; reviewing and investigation: Israa M Shamkh, Md Tabish Rehman; Khalid Ali Khan, Moayad Shahwan, Shimaa A. Ahmed and Imran Zafer: editing and supervision. All authors approved the final version of the manuscript.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

Additional information

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University Saudi Arabia for funding this work through Large Groups Project under grant [number RGP2/360/44].