RosettaCM for antibodies with very long HCDR3s and low template availability
Pranav Kodali1,2, Clara T Schoeder1,2, Samuel Schmitz1,2
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Proteins
|June 27, 2021
Summary
Computational antibody modeling is crucial for vaccine design. RosettaCM, a multi-template homology modeling protocol, shows improved accuracy for predicting antibody structures, especially those with long CDR-H3 regions.
Area of Science:
- Biomolecular modeling
- Structural biology
- Immunoinformatics
Background:
- Antibody-antigen co-crystal structures are vital for understanding immunity but laborious to determine.
- Homology modeling and docking are essential for antibody and vaccine design, with modeling quality being critical.
- Existing antibody modeling protocols include RosettaAntibody and AbPredict.
Purpose of the Study:
- To compare the performance of different computational protocols for predicting antibody structure from sequence.
- To evaluate if RosettaCM, a universal homology modeling protocol using multiple templates, improves antibody modeling accuracy over specialized methods.
- To investigate the impact of multi-template usage on antibody modeling, particularly for antibodies with long CDR-H3 regions.
Main Methods:
- Comparison of three modeling algorithms: RosettaAntibody, AbPredict, and RosettaCM.
- Utilizing RosettaCM, a multi-template comparative modeling protocol.
- Benchmarking against human antibodies from co-crystal structures.
Main Results:
- RosettaCM demonstrated superior performance in modeling antibody structures compared to RosettaAntibody and AbPredict.
- The improvement was most notable for antibodies characterized by long CDR-H3 regions and a limited number of available templates.
- Multi-template modeling within RosettaCM enhanced prediction accuracy.
Conclusions:
- RosettaCM offers improved accuracy for antibody structure prediction, particularly in challenging cases.
- Multi-template homology modeling is a promising strategy for enhancing antibody modeling pipelines.
- These findings support the use of RosettaCM for advancing antibody and vaccine design efforts.
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