Protein Homology Modelling

Introduction

        Protein homology modelling, also known as comparative modelling, is a computational technique used in bioinformatics to predict the three-dimensional structure of a protein based on its amino acid sequence and the known structure of a related protein (template).

Here's how it works:

• Sequence Alignment: Compare the sequence of the protein you want to model with proteins whose structures are already known.
• Template Selection: Choose a closely related protein with a known structure (the template) as a guide.
• Model Building: Use the template's structure to build a 3D model of the target protein, based on the alignment of their sequences.
• Model Refinement: Tweak the initial model to make it more accurate by adjusting its shape and structure.
• Validation: Check if the final model makes sense structurally and follows the rules of chemistry.
• Analysis and Interpretation: Study the modelled protein to understand its function and how it interacts with other molecules.

                Protein homology modelling is a valuable tool in structural biology and drug discovery, allowing researchers to study proteins' structure-function relationships, design novel therapeutics, and understand disease mechanisms at the molecular level. However, it's important to note that the accuracy of homology models depends on the quality of the sequence alignment, the suitability of the template structure, and the effectiveness of the modelling algorithms used.

Homology Modelling through Geno3D and Swiss Model:

1. Retrieve a protein sequence in FASTA Format.
2. Open Geno3D and go to its homepage.
3. Copy and paste the retrieved Sequence in the Geno3D Window.
4. There are two types of matrix/matrices:
1. BLOSUM (62)
2. PAM
5. Submit the sequences.
6. Select the most homologous sequence from the previous step's result. (at least 3 sequences)
7. After selecting, Provide the email and select how many models to be generated. (min-3 and max-10)
8. Run Geno3D.
9. Analyze the result, and visualize the structure and Ramachandran Plot.
10. Look at the energy section, who has the Lowest energy, it will be the most stable. (Normally value should be in minus).
11. If energy is (+)ve, structure isn't good.

There are two concepts in making a structure

• Experimental Structure
• Theoretical Structure 

Conclusion

Protein homology modelling helps us understand how proteins work and how they might be involved in diseases, guiding drug discovery and other research efforts.