The paper introduces a curriculum learning strategy for generative flexible docking, a task that predicts protein‑ligand complex configurations from an apo protein structure and a ligand SMILES string. By gradually incorporating examples with large conformational changes during training, the authors enhance an existing generative model, achieving a 46.52% top‑1 success rate on the PDBBind ESMFold apo benchmark and outperforming prior baselines. The approach leverages diffusion and flow‑based generative models to model the posterior distribution over ligand poses and protein conformations conditioned on the apo input.
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.
arXiv:2608.20366v1 Announce Type: cross Abstract: Molecular docking requires reasoning jointly about ligand pose and protein flexibility. Most diffusion-based docking models predict torsional updates...
arXiv:2607. 17412v1 Announce Type: new Abstract: A hallmark of neurodegenerative diseases such as Alzheimer's and Parkinson's is the aberrant aggregation of proteins into amyloid fibrils, and small molecules that selectively bind to these fibrils hold promise as diagnostics, imaging probes, and therapeutics.
arXiv:2610.04850v2 Announce Type: replace Abstract: Protein binding prediction is central to target identification, therapeutic binder design, and large scale screening, yet remains challenging becau...
Matcha is a new molecular docking method that refines ligand poses through three flow-matching stages—translation, rotation, and torsion—before applying GNINA for minimization, filtering, and ranking. It achieves high physical plausibility and is approximately 28 times faster than current large-scale co‑folding models, outperforming existing benchmarks. The authors provide code, benchmarking artifacts, and model checkpoints on GitHub and Zenodo.
arXiv:2607. 15309v1 Announce Type: cross Abstract: Proteins function through coordinated motion across multiple spatial and temporal scales, underpinning processes such as ligand binding, allostery, and catalysis.
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.
MLIPDiff is an inference‑time guidance technique that enhances pretrained denoising diffusion models for ligand generation by incorporating physics‑informed guidance from a machine‑learned interatomic potential (UMA). It combines four weighted energy terms—protein‑ligand interaction, ligand strain, steric clash, and pocket anchoring—to eliminate protein‑ligand collisions while preserving local geometry, without requiring model retraining. On the CrossDocked2020 benchmark, MLIPDiff produces clash‑free, physically plausible ligand poses and achieves superior binding‑affinity metrics compared to both the base diffusion model and NucleusDiff.
FuseDiff is an end‑to‑end diffusion model designed for dual‑target structure‑based drug design, jointly generating a ligand graph and two pocket‑specific binding poses conditioned on both target pockets. It employs a message‑passing backbone with Dual‑target Local Context Fusion (DLCF) to fuse ligand atom contexts from both pockets, preserving symmetry while enabling expressive joint modeling. The model enforces topological consistency across the two poses and allows target‑specific geometric adaptation, achieving state‑of‑the‑art docking performance and enabling systematic assessment of dual‑target pose quality before docking‑based pose search.
arXiv:2606. 08375v1 Announce Type: new Abstract: All-atom generative modeling of 3D biomolecular complexes has emerged as the dominant paradigm for predicting the structure of proteins and protein-ligand systems.
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.
The paper introduces LambdaDockScore, a protein‑protein docking scoring function that leverages the LambdaLoss loss from Learning‑to‑Rank to improve pose ranking. By fine‑tuning the energy prediction head of DFMDock on 2.9 million decoy poses from the DIPS dataset, LambdaDockScore outperforms the state‑of‑the‑art EuDockScore on CAPRI benchmark targets, achieving higher accuracy in top‑1 and top‑5 predictions. It also enhances ranking for antibody‑antigen and protein‑protein complexes with extreme binding interface sizes.