Skip to main content
The European High Performance Computing Joint Undertaking (EuroHPC JU)

Determinants for antibody specificity

Awarded Resources (in node hours)
Meluxina GPU
System Partition
13 November 2023 - 12 November 2024
Allocation Period

Antibodies can rapidly evolve in specific response to antigens. During the affinity maturation process the immune system produces antibodies with higher specificity and affinity in response to an antigen.

For a set of antibodies, we already observed that an increase in specificity can be accompanied by a rigidification of the binding site. The proposed project will use cutting-edge simulation techniques to obtain physically relevant conformational ensembles to characterise the antigen binding process and to identify determinants for antibody specificity. In addition, the project will investigate the role of different heavy and light chain pairings and framework residues on antigen binding.

The obtained results will provide determinants governing antibody specificity and help to advance antibody design. As starting structures for our simulations, the project will use available crystal structures and state-of-the-art antibody structure models, as the researchers are confident that the sampling can capture long time-scale rearrangements and functional conformational changes of the antigen binding site.

As the antigen-binding fragment contains approximately 500 residues, the required simulation time to capture essential conformational rearrangements of the binding site is enormous. Additionally, the programmes the project uses are GPU compatible and the methods we apply are easily parallelisable, making this project suitable for large scale supercomputers.