arXiv:2604. 24474v2 Announce Type: replace Abstract: Molecular similarity plays a central role in ligand-based drug discovery, such as virtual screening, analog searching, and goal-directed molecular generation.
arXiv:2606. 05198v1 Announce Type: cross Abstract: Nucleic acids are increasingly recognized as therapeutic targets beyond conventional protein-centered drug discovery, yet accurate and efficient docking of small molecules to nucleic acid structures remains challenging.
The study evaluates four pretrained molecular language models on six virtual libraries covering drug discovery, organic materials, and catalysis. It finds that native embeddings vary widely in performance, while molecular fingerprints remain consistently strong. Fine‑tuning the models on library‑specific data markedly improves sample efficiency, with several adapted encoders outperforming others across all tasks.
arXiv:2506. 14488v2 Announce Type: replace-cross Abstract: Structure-based drug design (SBDD) models are central to modern pharmaceutical research, enabling the rational exploration of protein-ligand interactions at atomic resolution.
The paper introduces ReGeoDTA, a framework that preserves chemical heterogeneity and continuous geometric relationships in drug and protein representations to improve drug–target affinity prediction. Experiments on three benchmark datasets show that maintaining representation fidelity consistently enhances predictive accuracy across various DTA architectures, while degrading representations harms performance and cannot be recovered by more complex downstream models. The study highlights representation fidelity as a key upstream design principle for accurate and generalizable affinity prediction.
arXiv:2506. 13196v5 Announce Type: replace Abstract: Accurate prediction of protein-ligand binding affinity is critical for drug discovery.
arXiv:2608. 02688v1 Announce Type: cross Abstract: Phenotypic drug discovery enables the discovery of functional relationships between molecular structures and cellular responses.
arXiv:2608. 13797v1 Announce Type: new Abstract: Computational approaches to drug discovery involve multiple sub-problems, and among them, drug-target binding affinity prediction plays an important role.
arXiv:2608. 05336v1 Announce Type: cross Abstract: Molecular representations are essential for the evaluation of molecular similarity and the development of structure-property relationships.
arXiv:2608. 19906v1 Announce Type: new Abstract: Accurately ranking active ligands for a target protein pocket from massive chemical libraries remains a central challenge in virtual screening.
arXiv:2607. 20550v1 Announce Type: cross Abstract: The traditional "one drug, one target" paradigm of structure-based drug design (SBDD) frequently proves inadequate for treating multifactorial diseases such as cancer and neurodegenerative disorders, owing to compensatory signaling pathways and the emergence of drug resistance.
The paper presents MoCoP v2, an enhanced contrastive pretraining method that aligns small molecule embeddings with deep‑learning‑derived cell morphology profiles. By replacing CellProfiler fingerprints with richer image‑encoded features, the new embeddings better capture how molecules alter cell morphology, leading to improved QSAR, toxicity, ADME, and activity predictions. Performance scales log‑linearly with training data size, indicating further gains with larger datasets.
NEAT-POCKET is a pocket‑conditioned extension of the autoregressive NEAT model that generates 3D molecules atom by atom within protein binding pockets, maintaining atom permutation invariance and explicitly modeling hydrogen atoms. It outperforms existing baselines on the CrossDocked and SPINDR datasets, achieving competitive structure‑based generation performance while sampling significantly faster. The model also supports pocket‑conditioned fragment completion, a capability directly useful for lead optimization and scaffold elaboration in drug design.