Computational Antibody Papers

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  • 2024-02-26

    Antigen-Specific Antibody Design and Optimization with Diffusion-Based Generative Models for Protein Structures

    • protein design
    • generative methods
    • structure prediction
    • Diffusion-based antibody-antigen binding site structural co-design
    • Sampling of antibody sequence and structure directly conditional on the antigen structure.
    • Model receives antigen structure and antibody framework in complex. Then CDRs are randomly initialized with AA types, orientations and positions.
    • The advantage over GANs and VAEs should be that it generates candidates iteratively so filters can be applied on the fly to the sampling process.
    • Diffusion probabilistic models learn to generate data via denoising samples from a prior distribution
    • They predict the amino acid type, ca coordinate and orientation in SO(3)
    • In addition to the joint design of sequences and structures, we can constrain partial states for other design tasks. For example, by fixing the backbone structure (positions and orientations) and sampling only sequences, we can do fix-backbone sequence design.
    • We cluster antibodies in the database according to CDR-H3 sequences at 50% sequence identity.
    • RMSD: is the Cα root-mean-square deviation (RMSD) between the generated structure and the original structure with only antibody frameworks aligned - however here higher RMSD means that the generated structure is more diverse.
    • However they also checked how accurate they are in RMSD when they fix sequences (so structure gets modified). Here for H3 they achieve 3.246 A.
    • AAR: is the amino acid recovery rate measured by the sequence identity between the reference CDR sequences and the generated sequences
    • They compared to RosettaAntibodyDesign by IMP (percentage of CDRs with better energy than the original cdr, AAR and Ca RMSD)
    • They optimize the antibody by perturbing it for several steps (forward diffusion) and then denoise it (going backwards) to find antibodies with better IMP but they also look at RMSD and Seq id.