ProbeMatchDTI introduces a probe-driven framework for drug‑target interaction prediction that preserves weak biochemical signals by using IterProbe to retain contextual states and BindingProbe to model cross‑entity complementarity at multiple scales. The method improves AUC‑ROC by 2.0% on BindingDB and 0.5% on DrugBank compared to prior biochemical representation learning approaches. Feature‑level analyses confirm the effectiveness of the probe-driven pattern matching, and the predictions are linked to an evidence‑guided downstream drug‑discovery workflow for candidate refinement and validation planning.
Drug synergy prediction estimates whether two drugs produce a stronger joint effect than expected from their individual activities. For drug combination discovery, a single synergy score is often not...
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.
By Yixiao Li, Yining Qian, Yefan Chen, Zenghui Chen, Jiayue Sun, Yuhai Zhao, Cheng Tan, An-Yang Lu
VINCENT is a post‑training framework that provides validated, chemically coherent explanations for drug synergy predictions by extracting atom‑pair evidence from attention and gradient signals, grouping them into motifs, and refining these motifs through repeated local perturbations. On a literature‑annotated subset of 25 drug pairs, VINCENT achieves a mean motif recall of 0.826, outperforming baselines (0.49–0.66). Across 71 test pairs, its validated interaction scores yield a TP/TN separation of 3.36, indicating more accurate recovery of literature‑supported molecular regions and better alignment with predictor behavior.
By Fan-Sheng Chuang, Xuchen Li, Yujing Bian, Kaixiong Zhou
arXiv:2607. 08404v1 Announce Type: cross Abstract: Current computational approaches for drug design typically focus on generating molecules conditioned on specific targets or general molecular properties, often neglecting the influence of disease context on target behavior and therapeutic outcomes.
By Ali Motahharynia, Mohammadreza Ghaffarzadeh-Esfahani, Mahsa Sheikholeslami, Navid Mazrouei, Matin Irajpour, Yousof Gheisari, Hajar Sirous
SpecOpt is a new molecular design task that optimizes the binding specificity of existing drugs by making constrained structural modifications. The method uses an agentic framework that docks a compound against its intended target and known off‑targets, compares residue‑aware atom‑protein contacts, and feeds the differential interactions to a large language model to propose changes. On a benchmark of 915 compounds, SpecOpt increased the target‑off‑target binding gap for 84.8% of cases while preserving drug‑like properties and structural similarity.
By Thao Nguyen, Heng Ji
arXiv:2609.37384v1 Announce Type: new
Abstract: Molecular representation learning is central to computer-aided drug discovery. Molecular graphs, SMILES strings, and 3D conformations provide complemen...
By Linqing Mo, Jiayu Zhou, Bin Chen
arXiv:2606. 14245v1 Announce Type: new Abstract: Drug-target interaction (DTI) and affinity (DTA) predictors increasingly achieve strong benchmark scores, yet their internal use of sequence, fingerprint, and graph features often remains opaque.
By Ali Vefghi, Zahed Rahmati, Mohammad Akbari
Monroe is a new molecular foundation model that improves upon existing models by pre‑training on over 81 million molecules from the PM6 quantum chemistry dataset, enhancing stereochemistry representation, and introducing novel training losses such as conformer denoising and embedding decorrelation. It also incorporates a prior‑data‑fitted model (TabPFN) for downstream in‑context prediction and demonstrates superior performance on Polaris benchmarks and activity cliff tests. Ablation studies show that the PFN‑based downstream approach can upgrade other models, producing state‑of‑the‑art variants MiniMol_PFN and CheMeleon_PFN.
By Blazej Banaszewski, Andrew W. Fitzgibbon
arXiv:2607. 25322v1 Announce Type: new Abstract: Multimodal drug discovery enables drug representation learning beyond chemical structure by incorporating cellular responses such as gene expression and cell morphology.
By Jintao Huang, Lu Leng, Ziyuan Yang
arXiv:2607. 17601v1 Announce Type: cross Abstract: Accurate protein-ligand binding affinity prediction is central to computational drug discovery, yet modern docking engines frequently disagree without indicating which prediction to trust.
By Yongchan Hong, Defu Cao, Wenjin Liu, Thomas Ku, Jordy Homing Lam, Emily Nguyen, Willie Neiswanger, Vsevolod Katritch, Yan Liu
The study investigates how different distribution shifts affect the evaluation of drug‑target affinity (DTA) models, using 718,800 drug‑protein pairs from ChEMBL and BindingDB. It compares a baseline Morgan‑fingerprint + protein‑CNN model with 12 architectures that combine four drug representations and three ESM‑2 interaction modes, finding that mean validation RMSE rises significantly under protein‑cluster and dual out‑of‑distribution (OOD) scenarios. Model rankings remain consistent across chemical shifts but diverge under protein and dual OOD, indicating that architecture selection depends on the specific extrapolation context rather than just average error or training‑set size.
Why it matters: The results suggest that DTA benchmarks should be designed to reflect the chemical and target shifts expected in real deployment, ensuring that chosen models perform reliably when applied to new chemical series or protein targets.
By Minjae Chung, Clara Li, Malar Paavai Muthukumaran, Shaunna Wang, Aniket Ramkrishnan Iyer, Shaun Qien Yeau Tan, Harinishree Sathu, Micky C. Nnamdi, J. Ben Tamo, Benoit Louis Marteau, May Dongmei Wang