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Protein Structure Prediction and Homology Modeling of Bcl-2-like Protein 1 from Gallus gallus

Overview

This project focuses on the structural prediction and homology modeling of the Bcl-2-like protein 1 from Gallus gallus (chicken). The study leverages multiple bioinformatics tools to predict the secondary structure of the protein and constructs a homology model using templates from closely related species. The primary goal is to gain insights into the structural and functional aspects of this protein, which plays a crucial role in apoptosis and other cellular processes.

Introduction

Bcl-2-like protein 1, encoded by the BCL2L1 gene, is a significant regulator of apoptosis in Gallus gallus. This project undertakes the prediction of its secondary structure and the development of a homology model to better understand its functional properties. The protein has known homologs in Mus musculus (mouse) and Homo sapiens (human), which serve as templates for homology modeling.

Methods

Secondary Structure Prediction

Three different methods were employed to predict the secondary structure of the Bcl-2-like protein 1:

  • Chou-Fasman Method:

    • Helices: 68.1%
    • Strands: 69.4%
    • Turns: 10.9%

  • GOR Method:

    • Helices: 40.61%
    • Strands: 27.94%
    • Turns: 21.39%
    • Coils: 10.04%

  • Neural Network Method:

    • Helices: 56.33%
    • Extended Strands: 6.11%
    • Random Coils: 37.55%

These predictions provide a comprehensive view of the likely secondary structure elements within the protein, highlighting regions of helices, strands, turns, and coils.

Homology Modeling

Homology modeling was performed using the following steps:

  1. Template Selection:

    • 1PQ1: Bcl-2-like protein 1 from Mus musculus (mouse) with 72.4% identity to the target sequence.
    • 1G5J: Bcl-2-like protein 1 from Homo sapiens (human) with 78.3% identity to the target sequence.

  2. Model Construction:

    • Using the Modeller tool integrated with Chimera, five models were generated for each template.
    • The model with the highest significance based on zDOPE scores and RMSD values was selected for further analysis.

  3. Model Validation:

    • The selected models were validated through RMSD comparisons and identity percentage assessments with the original templates.

Comparative Analysis

Comparative analysis was conducted between different models and templates:

  • Model-M (Mouse) vs. Model-H (Human):

    • RMSD: 1.449 Å
    • Identity: 61.56%

  • Model-M vs. Template-M:

    • RMSD: 0.206 Å
    • Identity: 61.22%

  • Model-H vs. Template-H:

    • RMSD: 0.474 Å
    • Identity: 76.00%

This analysis highlighted the structural similarities and differences between models derived from different species.

Multiple Sequence Alignment

Multiple Sequence Alignment (MSA) was performed using the following sequences:

  • Model-M (derived from Mus musculus)
  • Template-H (derived from Homo sapiens)
  • Model-H (derived from Homo sapiens)
  • Template-M (derived from Mus musculus)

The MSA provided insights into conserved regions across these sequences and further supported the selection of the most accurate model.

Results

The following are the key results from the project:

  1. Secondary Structure Prediction:

    • The secondary structure predictions from different methods were consistent with each other, providing a robust understanding of the protein's structural elements.

  2. Homology Modeling:

    • The final model based on the human template (Model-H) was found to be the most accurate, with an RMSD of 0.474 Å and an identity percentage of 76.00% when compared to the original human template.

  3. Comparative Analysis:

    • Model-H was determined to be the most suitable model for further studies due to its higher identity and lower RMSD values.

Discussion and Conclusion

The homology model derived from the human template (Model-H) is recommended for further research on the Bcl-2-like protein 1 from Gallus gallus. The higher identity percentage and favorable RMSD values indicate that this model best represents the protein's structure. This project demonstrates the importance of careful template selection in homology modeling, particularly when dealing with proteins involved in critical cellular processes like apoptosis.

References

  • UniProt: BCL-2-like protein 1 Q07816
  • RCSB PDB: 1G5J and 1PQ1
  • Hardwick, J. M., & Soane, L. (2013). BCL-2 family proteins in apoptosis and their role in cancer progression. Journal of Cell Science, 126(15), 3469-3477.
  • Martz, E. (2001). Homology Modeling for Beginners. Homology Modeling Workshop, UMass Amherst.