Multi-Task Genetic Algorithm with Multi-Granularity Encoding for Protein-Nucleotide Binding Site Prediction

Accurate identification of protein-nucleotide binding sites is fundamental to deciphering molecular mechanisms and accelerating drug discovery. However, current computational methods often struggle with suboptimal performance due to inadequate feature representation and rigid fusion mechanisms, which hinder the effective exploitation of cross-task information synergy. To bridge this gap, we propose MTGA-MGE, a framework that integrates a Multi-Task Genetic Algorithm with Multi-Granularity Encoding to enhance binding site prediction. Specifically, we develop a Multi-Granularity Encoding (MGE) network that synergizes multi-scale convolutions and self-attention mechanisms to distill discriminative signals from high-dimensional, redundant biological data. To overcome the constraints of static fusion, a genetic algorithm is employed to adaptively evolve task-specific fusion strategies, thereby effectively improving model generalization. Furthermore, to catalyze collaborative learning, we introduce an External-Neighborhood Mechanism (ENM) that leverages biological similarities to facilitate targeted information exchange across tasks. Extensive evaluations on fifteen nucleotide datasets demonstrate that MTGA-MGE not only establishes a new state-of-the-art in data-abundant, high-resource scenarios but also maintains a robust competitive edge in rare, low-resource regimes, presenting a highly adaptive scheme for decoding complex protein-ligand interactions in the post-genomic era.

LaPro-DTA: Latent Dual-View Drug Representations and Salient Protein Feature Extraction for Generalizable Drug--Target Affinity Prediction

Drug--target affinity prediction is pivotal for accelerating drug discovery, yet existing methods suffer from significant performance degradation in realistic cold-start scenarios (unseen drugs/targets/pairs), primarily driven by overfitting to training instances and information loss from irrelevant target sequences. In this paper, we propose LaPro-DTA, a framework designed to achieve robust and generalizable DTA prediction. To tackle overfitting, we devise a latent dual-view drug representation mechanism. It synergizes an instance-level view to capture fine-grained substructures with stochastic perturbation and a distribution-level view to distill generalized chemical scaffolds via semantic remapping, thereby enforcing the model to learn transferable structural rules rather than memorizing specific samples. To mitigate information loss, we introduce a salient protein feature extraction strategy using pattern-aware top-$k$ pooling, which effectively filters background noise and isolates high-response bioactive regions. Furthermore, a cross-view multi-head attention mechanism fuses these purified features to model comprehensive interactions. Extensive experiments on benchmark datasets demonstrate that LaPro-DTA significantly outperforms state-of-the-art methods, achieving an 8\% MSE reduction on the Davis dataset in the challenging unseen-drug setting, while offering interpretable insights into binding mechanisms.

Co-Diffusion: An Affinity-Aware Two-Stage Latent Diffusion Framework for Generalizable Drug-Target Affinity Prediction

Predicting drug-target affinity is fundamental to virtual screening and lead optimization. However, existing deep models often suffer from representation collapse in stringent cold-start regimes, where the scarcity of labels and domain shifts prevent the learning of transferable pharmacophores and binding motifs. In this paper, we propose Co-Diffusion, a novel affinity-aware framework that redefines DTA prediction as a constrained latent denoising process to enhance generalization. Co-Diffusion employs a two-stage paradigm: Stage I establishes an affinity-steered latent manifold by aligning drug and target embeddings under an explicit supervised objective, ensuring that the latent space reflects the intrinsic binding landscape. Stage II introduces modality-specific latent diffusion as a stochastic perturb-and-denoise regularizer, forcing the model to recover consistent affinity semantics from noisy structural representations. This approach effectively mitigates the reconstruction-regression conflict common in generative DTA models. Theoretically, we show that Co-Diffusion maximizes a variational lower bound on the joint likelihood of drug structures, protein sequences, and binding strength. Extensive experiments across multiple benchmarks demonstrate that Co-Diffusion significantly outperforms state-of-the-art baselines, particularly yielding superior zero-shot generalization on unseen molecular scaffolds and novel protein families-paving a robust path for in silico drug prioritization in unexplored chemical spaces.

CORE-Acu: Structured Reasoning Traces and Knowledge Graph Safety Verification for Acupuncture Clinical Decision Support

Large language models (LLMs) show significant potential for clinical decision support (CDS), yet their black-box nature -- characterized by untraceable reasoning and probabilistic hallucinations -- poses severe challenges in acupuncture, a field demanding rigorous interpretability and safety. To address this, we propose CORE-Acu, a neuro-symbolic framework for acupuncture clinical decision support that integrates Structured Chain-of-Thought (S-CoT) with knowledge graph (KG) safety verification. First, we construct the first acupuncture Structured Reasoning Trace dataset and a schema-constrained fine-tuning framework. By enforcing an explicit causal chain from pattern identification to treatment principles, treatment plans, and acupoint selection, we transform implicit Traditional Chinese Medicine (TCM) reasoning into interpretable generation constraints, mitigating the opacity of LLM-based CDS. Furthermore, we construct a TCM safety knowledge graph and establish a ``Generate--Verify--Revise'' closed-loop inference system based on a Symbolic Veto Mechanism, employing deterministic rules to intercept hallucinations and enforce hard safety boundaries. Finally, we introduce the Lexicon-Matched Entity-Reweighted Loss (LMERL), which corrects terminology drift caused by the frequency--importance mismatch in general optimization by adaptively amplifying gradient contributions of high-risk entities during fine-tuning. Experiments on 1,000 held-out cases demonstrate CORE-Acu's superior entity fidelity and reasoning quality. Crucially, CORE-Acu achieved 0/1,000 observed safety violations (95\% CI: 0--0.37\%), whereas GPT-4o exhibited an 8.5\% violation rate under identical rules. These results establish CORE-Acu as a robust neuro-symbolic framework for acupuncture clinical decision support, guaranteeing both reasoning auditability and strict safety compliance.