Fast and Accurate Antibody Sequence Design via Structure Retrieval
Track: Machine learning: computational method and/or computational results
Nature Biotechnology: No
Keywords: Antibody Design, Equivariant Graph Neural Networks
Abstract: Recent advancements in protein design have leveraged diffusion models to generate structural scaffolds, followed by a process known as protein inverse folding, which involves sequence inference on these scaffolds. However, these methodologies face significant challenges when applied to hyper-variable structures such as antibody Complementarity-Determining Regions (CDRs), where sequence inference frequently results in non-functional sequences due to hallucinations. Distinguished from prevailing protein inverse folding approaches, this paper introduces Igseek, a novel structure-retrieval framework that infers CDR sequences by retrieving similar structures from a natural antibody database. Specifically, Igseek employs a simple yet effective multi-channel equivariant graph neural network to generate high-quality geometric representations of CDR backbone structures. Subsequently, it aligns sequences of structurally similar CDRs and utilizes structurally conserved sequence motifs to enhance inference accuracy. Our experiments demonstrate that Igseek not only proves to be highly efficient in structural retrieval but also outperforms state-of-the-art approaches in sequence recovery for both antibodies and T-Cell Receptors, offering a new retrieval-based perspective for therapeutic protein design.
Anonymization: This submission has been anonymized for double-blind review via the removal of identifying information such as names, affiliations, and identifying URLs.
Presenter: ~Kun_XIE2
Format: Yes, the presenting author will attend in person if this work is accepted to the workshop.
Funding: Yes, the presenting author of this submission falls under ICLR’s funding aims, and funding would significantly impact their ability to attend the workshop in person.
Submission Number: 39
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