Yong Liu

Chenqing Hua, Jiarui Lu, Yong Liu et al.

The introduction of models like RFDiffusionAA, AlphaFold3, AlphaProteo, and Chai1 has revolutionized protein structure modeling and interaction prediction, primarily from a binding perspective, focusing on creating ideal lock-and-key models. However, these methods can fall short for enzyme-substrate interactions, where perfect binding models are rare, and induced fit states are more common. To address this, we shift to a functional perspective for enzyme design, where the enzyme function is defined by the reaction it catalyzes. Here, we introduce \textsc{GENzyme}, a \textit{de novo} enzyme design model that takes a catalytic reaction as input and generates the catalytic pocket, full enzyme structure, and enzyme-substrate binding complex. \textsc{GENzyme} is an end-to-end, three-staged model that integrates (1) a catalytic pocket generation and sequence co-design module, (2) a pocket inpainting and enzyme inverse folding module, and (3) a binding and screening module to optimize and predict enzyme-substrate complexes. The entire design process is driven by the catalytic reaction being targeted. This reaction-first approach allows for more accurate and biologically relevant enzyme design, potentially surpassing structure-based and binding-focused models in creating enzymes capable of catalyzing specific reactions. We provide \textsc{GENzyme} code at https://github.com/WillHua127/GENzyme.

Jialin Li, Qiang Nie, Weifu Fu et al.

Deep learning models, particularly those based on transformers, often employ numerous stacked structures, which possess identical architectures and perform similar functions. While effective, this stacking paradigm leads to a substantial increase in the number of parameters, posing challenges for practical applications. In today's landscape of increasingly large models, stacking depth can even reach dozens, further exacerbating this issue. To mitigate this problem, we introduce LORS (LOw-rank Residual Structure). LORS allows stacked modules to share the majority of parameters, requiring a much smaller number of unique ones per module to match or even surpass the performance of using entirely distinct ones, thereby significantly reducing parameter usage. We validate our method by applying it to the stacked decoders of a query-based object detector, and conduct extensive experiments on the widely used MS COCO dataset. Experimental results demonstrate the effectiveness of our method, as even with a 70\% reduction in the parameters of the decoder, our method still enables the model to achieve comparable or