Recent advances in structure-based drug design (SBDD) have produced surprising results, with models often generating molecules that achieve better Vina docking scores than actual ligands. However, these results are frequently overly optimistic due to the limitations of docking score accuracy and the challenges of wet-lab validation. While generated molecules may demonstrate high QED (drug-likeness) and SA (synthetic accessibility) scores, they often lack true drug-like properties or synthesizability. To address these limitations, we propose a model-level evaluation framework that emphasizes practical metrics aligned with real-world applications. Inspired by recent findings on the utility of generated molecules in ligand-based virtual screening, our framework evaluates SBDD models by their ability to produce molecules that effectively retrieve active compounds from chemical libraries via similarity-based searches. This approach provides a direct indication of therapeutic potential, bridging the gap between theoretical performance and real-world utility. Our experiments reveal that while SBDD models may excel in theoretical metrics like Vina scores, they often fall short in these practical metrics. By introducing this new evaluation strategy, we aim to enhance the relevance and impact of SBDD models for pharmaceutical research and development.

Text plays a crucial role in the transmission of human civilization, and teaching machines to generate online handwritten text in various styles presents an interesting and significant challenge. However, most prior work has concentrated on generating individual Chinese fonts, leaving complete text line generation largely unexplored. In this paper, we identify that text lines can naturally be divided into two components: layout and glyphs. Based on this division, we designed a text line layout generator coupled with a diffusion-based stylized font synthesizer to address this challenge hierarchically. More concretely, the layout generator performs in-context-like learning based on the text content and the provided style references to generate positions for each glyph autoregressively. Meanwhile, the font synthesizer which consists of a character embedding dictionary, a multi-scale calligraphy style encoder and a 1D U-Net based diffusion denoiser will generate each font on its position while imitating the calligraphy style extracted from the given style references. Qualitative and quantitative experiments on the CASIA-OLHWDB demonstrate that our method is capable of generating structurally correct and indistinguishable imitation samples.

In the field of Structure-based Drug Design (SBDD), deep learning-based generative models have achieved outstanding performance in terms of docking score. However, further study shows that the existing molecular generative methods and docking scores both have lacked consideration in terms of specificity, which means that generated molecules bind to almost every protein pocket with high affinity. To address this, we introduce the Delta Score, a new metric for evaluating the specificity of molecular binding. To further incorporate this insight for generation, we develop an innovative energy-guided approach using contrastive learning, with active compounds as decoys, to direct generative models toward creating molecules with high specificity. Our empirical results show that this method not only enhances the delta score but also maintains or improves traditional docking scores, successfully bridging the gap between SBDD and real-world needs.