Homology modeling has become a popular method for predicting protein structure based on the amino acid sequence of a protein and the existing structure of related proteins. Homology modeling can be a powerful tool for drug discovery because it allows researchers to assess how a potential drug interacts with a target protein. However, it is critical to assess the quality of the generated homology models to ensure their reliability and accuracy.Discovery Studio is a software suite widely used by researchers in the field of computational drug discovery. In this article, we will discuss some of the tutorials available in Discovery Studio for evaluating models after homology modeling.
The Ramachandran plot is used to evaluate the plausibility of the backbone conformation of two adjacent peptide units by the minimum contact distance between non-bonded atoms in the protein, and to indicate the allowed and disallowed conformations in the protein, and the number of amino acids located in the disallowed region should be less than 5% of the total number of amino acids.
After importing the protein structure to be evaluated, from the main menu, select Chart>Ramachandran Plot to display the pull-down plot of the model.
Profile-3D is a model evaluation procedure based on the "threading" method developed by Professor David Eisenberg at UCLA. The method uses a 3D-1D scoring function to test the relationship between the constructed model and its own amino acid sequence. The higher the score, the higher the confidence of the homologous model.
In the toolbar, click Macromolecules>Create Homology Models>Verify Protein (Profile-3D) to open the Verify Protein (Profile-3D) dialog box.
Click on the grid to the right of Input Protein Molecules and select 6njs:Visible (models to be evaluated).
Click Run to run the task. When the task is completed, the Verify Score scoring window pops up.
In the file browser, click Samples>Tutorials>QSAR, and double-click trainingset.sd to import the 14 molecules of the training set required for this tutorial.
Another important aspect of evaluating homology models is assessing the overall quality of the protein structure. one of the tools available in Discovery Studio for this purpose is the "Validate Protein Structure" protocol. This protocol calculates a structural quality score based on various parameters, including bond length, bond angle, and torsion angle.
In summary, homology models are a popular and useful method for predicting the structure of proteins that have not yet been experimentally determined. However, it is critical to assess the quality of the generated models to ensure their reliability and accuracy. Discovery Studio provides several tools and protocols for evaluating homology models, including Ramachandran plot analysis, verify protein structures, and Profile-3D assessment model method. By using these tools, researchers can improve the accuracy and reliability of their homology models and make more informed predictions about potential drug targets.