Generative Co-Design of Antibody Sequences and Structures via Black-Box Guidance in a Shared Latent Space
Year: 2025
Type: preprint
Abstract: Advancements in deep generative models have enabled the joint modeling of antibody sequence and structure, given the antigen-antibody complex as context. However, existing approaches for optimizing complementarity-determining regions (CDRs) to improve developability properties operate in the raw data space, leading to excessively costly evaluations due to the inefficient search process. To address this, we propose LatEnt blAck-box Design (LEAD), a sequence-structure co-design framework that optimizes both sequence and structure within their shared latent space. Optimizing shared latent codes can not only break through the limitations of existing methods, but also ensure synchronization of different modality designs. Particularly, we design a black-box guidance strategy to accommodate real-world scenarios where many property evaluators are non-differentiable. Experimental results demonstrate that our LEAD achieves superior optimization performance for both single and multi-property objectives. Notably, LEAD reduces query consumption by a half while surpassing baseline methods in property optimization. The code is available at https://github.com/EvaFlower/LatEnt-blAck-box-Design.
Source: arXiv (Cornell University)
Authors: Yao, Yinghua, Pan, Yuangang, Chen, Xixian
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7075993817
Cites:
Cited by:
Related to: