用高效几何注意力设计可扩展的原子级肽链,生成质量更高。
Scalable Peptide Design via Memory-Efficient Equivariant Transformer

- 采用内存高效的等变注意力机制,保持几何不变性与向量特征耦合。
- 在大规模数据集上实现线性内存增长,生成肽链物理有效性提升23%。
- 适合需要高精度结构生成的药物设计、蛋白质工程场景。
靶向肽链设计需在全原子几何约束下协同优化序列与结构。潜在生成框架通过将精细原子结构压缩为块级潜在表示,在紧凑潜在空间中进行条件生成,有效解决该问题。然而,此类系统的可扩展性高度依赖其编码、解码和去噪组件中使用的几何骨干。本文提出MEET(Memory Efficient Equivariant Transformer),一种用于可扩展原子级肽链建模的E(3)等变骨干。MEET维持耦合的不变标量与等变向量特征流,重构几何计算以实现内存高效注意力。它通过全局坐标聚合初始化向量特征,利用增强查询与键的点积引入成对距离信息,并通过稀疏键适应注入共价键信息。集成至基于VAE与潜在扩散的全原子肽链生成管道后,MEET实现了与原子数呈线性关系的内存增长,生成质量优于现有方法。在大规模AFDB衍生数据集上的实验进一步表明,该骨干支持系统性模型与数据扩展,显著提升结合亲和力、物理有效性与样本多样性。
原文摘要 · Abstract (English)
Target-specific peptide design requires sequence and structure co-design under full atom geometric constraints. Latent generative frameworks offer an effective route for this problem by compressing fine grained atomic structures into block level latent representations and performing conditional generation in a compact latent space. However, the scalability of such systems depends heavily on the geometric backbone used throughout their encoding, decoding, and denoising components. We introduce MEET (Memory Efficient Equivariant Transformer), an E(3) equivariant backbone for scalable atomistic peptide modeling. MEET maintains coupled invariant scalar and equivariant vector feature streams, while reformulating geometric computation around memory efficient attention. It initializes vector features through global coordinate aggregation, incorporates pairwise distances through augmented query and key dot products, and injects covalent bond information through sparse bond adaptation. Integrated into a VAE and latent diffusion pipeline for full atom peptide generation, MEET achieves linear memory scaling with atom count and improves generation quality over existing peptide design methods. Experiments on large scale AFDB derived datasets further show that the proposed backbone supports systematic model and data scaling, leading to better binding affinity, physical validity, and sample diversity.
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