In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer

Hafiz Muhammad Rehman; Hafiz Muzzammel Rehman; Muhammad Naveed; Muhammad Tahir Khan; Muhammad Aqib Shabbir; Shakira Aslam; Hamid Bashir

doi:10.1177/11779322231182560

In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer

Bioinform Biol Insights. 2023 Jun 23:17:11779322231182560. doi: 10.1177/11779322231182560. eCollection 2023.

Authors

Hafiz Muhammad Rehman^{1

2}, Hafiz Muzzammel Rehman^{3

4}, Muhammad Naveed⁵, Muhammad Tahir Khan⁶, Muhammad Aqib Shabbir⁵, Shakira Aslam¹, Hamid Bashir¹

Affiliations

¹ Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan.
² University Institute of Medical Lab Technology, Faculty of Allied Health Sciences, The University of Lahore, Pakistan.
³ School of Biochemistry & Biotechnology, University of the Punjab, Lahore, Pakistan.
⁴ Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan.
⁵ Department of Biotechnology, Faculty of Science & Technology, University of Central Punjab, Lahore, Pakistan.
⁶ Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

Abstract

Targeted delivery of therapeutic anticancer chimeric molecules enhances the efficacy of drug by improving cellular uptake and circulation time. Engineering the molecules to facilitate the specific interaction between chimeric protein and its receptor is critical to elucidate biological mechanism as well as accuracy in modeling of complexes. A theoretically designed novel protein-protein interfaces can serve as a bottom-up method for comprehensive understanding of interacting protein residues. This study was aimed for in silico analyses of a chimeric fusion protein against breast cancer. The amino acid sequences of the interleukin 24 (IL-24) and LK-6 peptide were used to design the chimeric fusion protein via a rigid linker. The secondary and tertiary structures along with physicochemical properties by ProtParam and solubility were predicted using online software. The validation and quality of the fusion protein was confirmed by Rampage and ERRAT2. The newly designed fusion construct has a total length of 179 amino acids. The top-ranked structure from alpha fold2 showed 18.1 KD molecular weight by ProtParam, quality factor of 94.152 by ERRAT, and a valid structure by a Ramachandran plot with 88.5% residues in the favored region. Finally, the docking and simulation studies were performed using HADDOCK and Desmond module of Schrodinger. The quality, validity, interaction analysis, and stability of the fusion protein depict a functional molecule. The fusion gene IL24-LK6 after cloning and expression in a suitable prokaryotic cell might be a useful candidate for developing a novel anticancer therapy.

Keywords: Interleukin 24; LK-6; fusion protein; molecular docking.