The paper introduces PIFT, a framework that transfers peptide‑target interaction patterns to small molecules by jointly guiding masked discrete diffusion and continuous flow matching. PIFT maps peptide‑target and small‑molecule‑target interfaces into a shared, target‑conditioned interaction space, enabling peptide‑derived references to steer both building‑block logits and 3D coordinates toward peptide‑compatible molecules while maintaining a strong molecular prior. Experiments on diverse protein‑protein interaction targets demonstrate that this cross‑modal representation improves interface recovery, docking performance, and molecular properties.
arXiv:2610.14699v1 Announce Type: new Abstract: The design of high-affinity, target-specific protein binders is central to the development of modern therapeutics. However, existing protein-generation...
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.
arXiv:2606. 27824v1 Announce Type: cross Abstract: Peptides are a promising therapeutic modality that combine the chemical tunability of small molecules with the target specificity of macromolecular therapeutics.
arXiv:2608.21367v1 Announce Type: cross Abstract: Protein-peptide interactions are central to cellular regulation and peptide-based drug discovery, yet existing computational methods mainly focus on...
arXiv:2607. 18144v1 Announce Type: cross Abstract: Structure-based drug design (SBDD) leverages the 3D structure of protein targets, often complemented by other spatial constraints, to generate candidate binding molecules.
arXiv:2606. 06717v1 Announce Type: cross Abstract: While generative AI models have demonstrated remarkable success in structure-based drug design, they predominantly rely on deep binding pockets and struggle to sample effective ligands for challenging low-pocketability targets, such as the historically "undruggable" oncology targets KRAS and MYC.
arXiv:2607. 01105v1 Announce Type: new Abstract: We present SynLaD, a latent diffusion framework for small-molecule generation that unifies ligand-based drug design objectives (what to make) with synthetic accessibility (how to make it).
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.
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.
arXiv:2606. 23856v1 Announce Type: new Abstract: Generative molecular models for drug design are a promising direction with much active research.
SupraTITO is a transferable generative molecular dynamics framework designed for supramolecular systems, specifically peptide self‑assembly. It learns implicit transfer operators conditioned on peptide sequence, molecular topology, and periodic geometry, enabling the propagation of configurations over time intervals far longer than a single MD step. On a dipeptide benchmark, SupraTITO generalizes to unseen sequences, accurately reproduces sequence‑dependent structures and dynamics, and maintains molecular integrity over long rollouts, outperforming direct ensemble prediction models.