Computational Design and Evaluation of scFv-DSH2a as a PSMA-Targeted Immunotoxin for Prostate Cancer Therapy Computational design of scFv-DSH2a as a PSMA-targeted immunotoxin
Trends in Peptide and Protein Sciences,
Vol. 10 No. 1 (2025),
16 March 2025
,
Page 1-13 (e3)
https://doi.org/10.22037/tpps.v10i1.50730
Abstract
Prostate cancer is one of the most prevalent malignancies in men and a leading cause of cancer-related mortality. The prostate-specific membrane antigen (PSMA), which is highly overexpressed in prostate tumors and internalized upon ligand binding, represents a promising target for immunotoxin-based therapies. In this study, a novel chimeric immunotoxin, scFv-DSH2a, using bioinformatics tools, was designed to selectively target PSMA-expressing cells. The construct was generated by fusing the single-chain variable fragment (scFv) of the J591 antibody to the cytotoxic DELTA-stichotoxin-Hmg2a (DSH2a) via a flexible linker. Structural modeling and refinement were performed using GalaxyWEB and Galaxy Refine, and the model was validated through PROCHECK and ProSA-web. Physicochemical properties were assessed using ProtParam, solubility predicted via SOLpro, and allergenicity evaluated using AllerTOP v.2.0. Protein–protein docking with PSMA was conducted using ClusPro, and molecular dynamics simulations were performed with GROMACS to assess complex stability. The designed immunotoxin exhibited favorable stability (instability index: 32.72), solubility (probability: 0.624), and non-allergenic properties. Docking results revealed strong binding affinity to PSMA, and molecular dynamics simulations confirmed structural stability over 100 nanoseconds, with low root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values and consistent radius of gyration. These findings suggest that scFv-DSH2a is a promising candidate for targeted immunotherapy in prostate cancer, offering specificity, stability, and potential safety for future therapeutic development.
HIGHLIGHTS
- A novel immunotoxin (scFv-DSH2a) was designed to target PSMA in prostate cancer.
- Bioinformatics tools confirmed its stability, solubility, and non-allergenicity.
- Molecular docking showed strong binding affinity to PSMA.
- Molecular dynamics simulations confirmed complex stability over 100 ns.
- scFv-DSH2a is a promising candidate for targeted prostate cancer immunotherapy.
- Bioinformatics
- Immunotoxin
- Prostate cancer
- PSMA
How to Cite
References
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