EnzyPGM: Pocket-conditioned Generative Model for Substrate-specific Enzyme Design

Designing enzymes with substrate-binding pockets is a critical challenge in protein engineering, as catalytic activity depends on the precise interaction between pockets and substrates. Currently, generative models dominate functional protein design but cannot model pocket-substrate interactions, which limits the generation of enzymes with precise catalytic environments. To address this issue, we propose EnzyPGM, a unified framework that jointly generates enzymes and substrate-binding pockets conditioned on functional priors and substrates, with a particular focus on learning accurate pocket-substrate interactions. At its core, EnzyPGM includes two main modules: a Residue-atom Bi-scale Attention (RBA) that jointly models intra-residue dependencies and fine-grained interactions between pocket residues and substrate atoms, and a Residue Function Fusion (RFF) that incorporates enzyme function priors into residue representations. Also, we curate EnzyPock, an enzyme-pocket dataset comprising 83,062 enzyme-substrate pairs across 1,036 four-level enzyme families. Extensive experiments demonstrate that EnzyPGM achieves state-of-the-art performance on EnzyPock. Notably, EnzyPGM reduces the average binding energy of 0.47 kcal/mol over EnzyGen, showing its superior performance on substrate-specific enzyme design. The code and dataset will be released later.

R$^2$: A LLM Based Novel-to-Screenplay Generation Framework with Causal Plot Graphs

Automatically adapting novels into screenplays is important for the TV, film, or opera industries to promote products with low costs. The strong performances of large language models (LLMs) in long-text generation call us to propose a LLM based framework Reader-Rewriter (R$^2$) for this task. However, there are two fundamental challenges here. First, the LLM hallucinations may cause inconsistent plot extraction and screenplay generation. Second, the causality-embedded plot lines should be effectively extracted for coherent rewriting. Therefore, two corresponding tactics are proposed: 1) A hallucination-aware refinement method (HAR) to iteratively discover and eliminate the affections of hallucinations; and 2) a causal plot-graph construction method (CPC) based on a greedy cycle-breaking algorithm to efficiently construct plot lines with event causalities. Recruiting those efficient techniques, R$^2$ utilizes two modules to mimic the human screenplay rewriting process: The Reader module adopts a sliding window and CPC to build the causal plot graphs, while the Rewriter module generates first the scene outlines based on the graphs and then the screenplays. HAR is integrated into both modules for accurate inferences of LLMs. Experimental results demonstrate the superiority of R$^2$, which substantially outperforms three existing approaches (51.3%, 22.6%, and 57.1% absolute increases) in pairwise comparison at the overall win rate for GPT-4o.