Structural and functional analysis of engineered antibodies for cancer immunotherapy: insights into protein compactness and solvent accessibility

Abstract

Antibodies are crucial tools in various biomedical applications, including immunotherapy. In this study, we focused on designing and engineering antibodies to enhance their structural dynamics and functional properties. By employing advanced computational techniques and experimental validation, we gained crucial insights into the impact of specific mutations on the engineered antibodies. This study investigates the design and engineering of antibodies to improve their structural dynamics and functional properties. Structural attributes, such as protein compactness and solvent accessibility, were assessed, revealing interesting trends in anti-CD3 and anti-HER2 antibodies. Mutations in CD3 antibodies resulted in a more stable conformation, while mutant HER2 antibodies exhibited altered interaction with the target. Analysis of secondary structure assignments demonstrated significant changes in the folding and stability of the mutant antibodies compared to the wild-type counterparts. The conformational landscape of the engineered antibodies was explored, providing insights into folding pathways and binding mechanisms. Overall, the current study highlights the significance of antibody design and engineering in modulating structural dynamics and functional properties. The findings contribute to developing improved immunotherapeutic strategies by optimising antibody-based therapeutics for targeted diseases with enhanced efficacy and precision.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cancer
• HER2
• CD3
• molecular dynamics simulation
• immunotherapy
• bi-specific antibody

Acknowledgements

All authors thank Dell EMC HPC & AI Innovation Lab, Bangalore, for providing access to high-performance computing facilities and GROMACS modules.

Ethical approval and consent to participate

As a computational study, this research does not involve human participants, biological samples or personal data. The study solely relies on publicly available data, existing literature or simulated models for analysis and interpretation.

Consent for publication

I affirm that the manuscript represents original work, and all co-authors have been appropriately acknowledged and included. I confirm that all individuals who have made significant contributions to the study are listed as authors and that all listed authors have reviewed and approved the final version of the manuscript.

Competing interests

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author contributions

SS and YK jointly developed the conceptual framework for the study. SS took charge of designing the study executing mutagenesis, modelling and docking experiments. SS also prepared the tables and figures and authored the manuscript. SS compiled the manuscript, while SS and YK contributed to data analysis. YK provided guidance, reviewed and made revisions to the manuscript. All authors critically reviewed and approved the final version of the manuscript.

Additional information

Funding

This study received funding from the Department of Science and Technology (DST) - Science and Engineering Research Board (SERB) [ECR/2016/001752], which was granted to YK. SS was supported by a Junior Research Fellowship awarded by the Department of Science and Technology (DST) - Science and Engineering Research Board (SERB) [ECR/2016/001752].