Basic Methodology to Predict Antigen-Antibody Interactions in silico

Antigen-antibody interactions play an important role in protecting our body from foreign molecules. This is applied in vaccine development against a disease. In this article, we are going to mention a simple methodology used in studying/ identifying interactions between antigen-antibody complex.

The basic methodology includes:

1. Structure prediction of antigen
2. Structure prediction of antibody
3. Docking of antigen-antibody
4. Analysis
5. Molecular Dynamics (MD) Simulation

1. Structure prediction of antigen

Predict a 3D structure of your antigen of interest using some software such as:

• IEDB Analysis (http://tools.iedb.org/main/bcell/)
• LYRA (http://tools.iedb.org/lyra/)

2. Structure Prediction of antibody

Predict a 3D structure of the antibody using some software such as:

• RosettaAntibody3 (https://www.rosettacommons.org/docs/latest/application_documentation/antibody/antibody-protocol)
• RosettaAntibodyDesign (RAbD) (https://new.rosettacommons.org/docs/latest/application_documentation/antibody/RosettaAntibodyDesign)
• SaBPred (http://opig.stats.ox.ac.uk/webapps/newsabdab/sabpred/)

3. Docking of antigen-antibody

Now, since you have the structures of antigen and antibody, you can go for their docking. For docking of antigen-antibody complex, you can use:

• HADDOCK2.4 web server (https://wenmr.science.uu.nl/haddock2.4/)
• Cluspro2.0 (https://cluspro.bu.edu/login.php)
• ZDOCK (https://zdock.umassmed.edu/)
• LightDock (https://lightdock.org/)

Amongst the above-mentioned tools, HADDOCK provides the best results with high-accuracy models [1].

4. Analysis

For analysis of docking results, you can use software such as Pymol, Discovery Studio Visualizer, Chimera, and so on. Some web servers such as HADDOCK provide a script that you can run in software like Pymol to directly visualize the antigen-antibody interactions.

5. MD Simulation

After successful docking, you should go for an MD simulation of the antigen-antibody complex. It will help you to analyze the stability of the complex. Set an appropriate timescale and other parameters for MD run.

This is a basic methodology explained in this tutorial. You can always go for advanced docking considering all parameters including homology modeling or ab initio prediction of antigen and antibody structures.

References

1. Ambrosetti, F., Jiménez-García, B., Roel-Touris, J., & Bonvin, A. M. (2020). Modeling antibody-antigen complexes by information-driven docking. Structure, 28(1), 119-129.