Wenzhi Xiao

Cong Liu, Milong Ren, Jiaqi Guan et al.

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We introduce ProtDBench, a standardized and throughput-aware evaluation framework for protein binder design. ProtDBench defines unified benchmark tasks, evaluation protocols, and success criteria, enabling systematic analysis of how evaluation design influences observed performance. Using a large wet-lab annotated dataset, we analyze commonly used structure prediction models as evaluation verifiers, revealing substantial verifier-dependent bias and limited agreement under identical filtering protocols. We then benchmark representative open-source generative binder design methods across ten diverse protein targets under a fixed evaluation protocol. Beyond per-sequence success rates, ProtDBench incorporates throughput-aware metrics based on a fixed 24-hour budget, as well as cluster-level success criteria to account for structural diversity. Together, these results expose systematic differences induced by filtering rules, success definitions, and throughput-aware evaluation between computational efficiency, success rate, and structural diversity. Overall, ProtDBench provides a fair and reproducible evaluation pipeline that supports systematic and controlled comparison of protein binder design methods under realistic evaluation settings.

Chaoran Cheng, Jiaqi Guan, Milong Ren et al.

We present A-CODE, a fully atomic unified one-stage protein co-design model that simultaneously refines discrete atom types and continuous atom coordinates. Unlike predominant two-stage methods that cascade structure design with amino acid-level sequence design, our approach is fully atomic within a unified multimodal diffusion framework, in which residue identities are inferred solely from atom-level predictions. Built upon the powerful all-atom architecture, A-CODE achieves superior designability for unconditional protein generation, outperforming all existing one-stage and two-stage design models. For binder design, A-CODE rivals and even outperforms existing state-of-the-art two-stage design models and, compared with the existing one-stage co-design model, achieves a drastic tenfold improvement in success rate on hard tasks. The inherent flexibility of our atomic formulation enables, for the first time, seamless adaptation to non-canonical amino acid (ncAA) modeling. Our fully atomic framework establishes a new, versatile foundation for all-atom generative modeling that can be naturally extended to complex biomolecular systems.

Weihao Gao, Xiangjun Fan, Chong Wang et al.

One of the core problems in large-scale recommendations is to retrieve top relevant candidates accurately and efficiently, preferably in sub-linear time. Previous approaches are mostly based on a two-step procedure: first learn an inner-product model, and then use some approximate nearest neighbor (ANN) search algorithm to find top candidates. In this paper, we present Deep Retrieval (DR), to learn a retrievable structure directly with user-item interaction data (e.g. clicks) without resorting to the Euclidean space assumption in ANN algorithms. DR's structure encodes all candidate items into a discrete latent space. Those latent codes for the candidates are model parameters and learnt together with other neural network parameters to maximize the same objective function. With the model learnt, a beam search over the structure is performed to retrieve the top candidates for reranking. Empirically, we first demonstrate that DR, with sub-linear computational complexity, can achieve almost the same accuracy as the brute-force baseline on two public datasets. Moreover, we show that, in a live production recommendation system, a deployed DR approach significantly outperforms a well-tuned ANN baseline in terms of engagement metrics. To the best of our knowledge, DR is among the first non-ANN algorithms successfully deployed at the scale of hundreds of millions of items for industrial recommendation systems.