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<p>DDR2 (Discoidin Domain Receptor 2) is a receptor tyrosine kinase that regulates essential cellular processes such as proliferation, differentiation, invasion, and migration by triggering downstream signaling cascades. Located on the long arm of chromosome 1, DDR2 has been implicated in several malignancies, including lung, ovarian, breast, and prostate cancers. This study aimed to identify and characterize a novel alternatively spliced transcript of the DDR2 gene through a combined bioinformatics and experimental approach. Sequence analysis revealed a previously unreported intronic region between coding exons 1 and 2 containing a start codon, suggesting its potential to encode a distinct N-terminal variant. Expression of this novel transcript was validated in prostate and lung tissues using RT-PCR and Sanger sequencing. The translated sequence was analyzed for physicochemical properties such as molecular weight, isoelectric point, and predicted half-life. Structural models for both canonical and novel DDR2 isoforms were generated using MODELLER 10.4 with PDB ID: 4AG4 as a template. Molecular docking with known DDR2 inhibitors followed by molecular dynamics simulations was performed to assess stability and interaction dynamics. Analyses of RMSD, RMSF, radius of gyration, solvent-accessible surface area (SASA), secondary structure (DSSP), and hydrogen bonding provided detailed insights into conformational behavior. The objective of this work was to uncover structural and functional diversity within DDR2 arising from alternative splicing. The significance lies in revealing a potential variant associated with prostate cancer progression, offering new molecular insights that may aid in the design of targeted DDR2-based therapeutic strategies.</p>

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Identification and In Silico Characterization of an Alternatively Spliced Novel Transcript of Human DDR2 Gene

  • 期刊论文

  • 发表日期：

    2025年11月1日

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  • Akshat Rathi,
  • Faizan Abul Qais,
  • Naira Rashid,
  • Faizan Ahmad,
  • Sayeed ur Rehman

摘要

DDR2 (Discoidin Domain Receptor 2) is a receptor tyrosine kinase that regulates essential cellular processes such as proliferation, differentiation, invasion, and migration by triggering downstream signaling cascades. Located on the long arm of chromosome 1, DDR2 has been implicated in several malignancies, including lung, ovarian, breast, and prostate cancers. This study aimed to identify and characterize a novel alternatively spliced transcript of the DDR2 gene through a combined bioinformatics and experimental approach. Sequence analysis revealed a previously unreported intronic region between coding exons 1 and 2 containing a start codon, suggesting its potential to encode a distinct N-terminal variant. Expression of this novel transcript was validated in prostate and lung tissues using RT-PCR and Sanger sequencing. The translated sequence was analyzed for physicochemical properties such as molecular weight, isoelectric point, and predicted half-life. Structural models for both canonical and novel DDR2 isoforms were generated using MODELLER 10.4 with PDB ID: 4AG4 as a template. Molecular docking with known DDR2 inhibitors followed by molecular dynamics simulations was performed to assess stability and interaction dynamics. Analyses of RMSD, RMSF, radius of gyration, solvent-accessible surface area (SASA), secondary structure (DSSP), and hydrogen bonding provided detailed insights into conformational behavior. The objective of this work was to uncover structural and functional diversity within DDR2 arising from alternative splicing. The significance lies in revealing a potential variant associated with prostate cancer progression, offering new molecular insights that may aid in the design of targeted DDR2-based therapeutic strategies.