Delineating SARS-CoV-2 spike protein and antibodies interaction interfaces via siamese neural networks: A geometric...

The analysis of molecular interactions between antigens and antibodies is crucial for understanding the immunological mechanisms underlying the immune response and for developing effective therapies against various diseases. In this context, the ability to distinguish between protein interfaces that form stable and unstable complexes is a key step in the design of therapeutic antibodies and vaccines. In recent years, deep learning models have provided advanced tools for biomedical research. This work introduces a novel approach to analyzing antibody-antigen interactions, and in particular SARS-CoV-2 spike protein-targeting antibodies, using a Siamese Neural Network specifically designed to integrate depth maps with geometric descriptors of molecular surfaces. By combining these representations, the model captures geometrical shape complementarity to differentiate between stable and unstable protein complexes. The network was trained using image-based representations of antigens and antibodies interfaces enriched with geometric descriptors, using data that include binders and non-binders of the SARS-CoV-2 spike protein receptor-binding domain. The deep learning network operates by comparing feature vectors representing these molecular surfaces; pairs with closer vectors in feature space are associated with stable interactions, while those with more distant vectors suggest instability. Extensive testing with different configurations achieved an accuracy of 90%, demonstrating the robustness of this approach to predict interactions. This innovative integration of artificial intelligence, depth maps and geometric descriptors offers promising applications for designing novel antibodies and vaccines.