arXiv subjects

Wooyeol Lee

Publications and source records attributed to Wooyeol Lee.

6 recordsLinked to original sources

arXiv2026

Complete Donor-Set Guidance for Frozen Diffusion Docking Models

Metalloprotein docking requires a ligand pose to satisfy both global pocket fit and the identity and geometry of metal-coordinating atoms. General-purpose diffusion docking models do not explicitly condition generation on externally specified complete ligand donor sets, and their predicted poses can exhibit incorrect metal-donor relationships. Metal-aware models address coordination during training and generation; here we ask whether external donor information can correct already-trained general-purpose models without retraining. We propose Complete-Identity Contract Guidance (CICG), which applies a supplied complete donor set through translation, rotation, and torsion updates, and Historical Contract Transfer (HCT), which supplies donor identities from earlier complexes at compatible receptor sites. We compare HCT with trajectory-local controls retaining the historical donor count with or without elemental composition. On 86 assessable HCT-covered queries, HCT-guided CICG increases frozen-confidence-selected joint success from 21.5% to 36.6% on SurfDock and from 25.0% to 34.9% on DiffDock-L. The joint criterion requires correct global ligand placement, complete native donor recovery, coordination geometry, preserved stereochemistry, and absence of fatal receptor clashes. Composition-matched guidance reaches 33.14% and 34.30%, leaving the additional benefit of fixed historical membership unresolved. Our results therefore support donor-set guidance as a conditional correction for frozen docking models, while identifying donor-source reliability and physical-quality preservation as the main barriers to broader use.

physics.chem-ph↗

arXiv2026

Risk-Calibrated Proposal Transport for Finite-Particle Diffusion Steering

Inference-time steering combines pretrained diffusion experts or rewards without retraining by changing the dynamics that transport noise to data. Feynman-Kac correction compensates for proposal mismatch through importance-weighted sequential Monte Carlo (SMC), whose finite-particle behavior depends on the proposal. Variance-controlling guidance (VCG) improves that proposal by fitting a linear drift correction to minimize empirical log-weight-rate variance. Although its population optimum cannot worsen residual variance, finite-particle VCG can nearly eliminate its fitting residual while increasing residual risk on new states by orders of magnitude. The resulting update can degrade unweighted generation or accelerate particle collapse. We show that the centered Feynman-Kac rate is the normalized transport residual and that expected out-of-fit benefit is exactly population headroom minus coefficient-estimation penalty. Under regularity assumptions, a Wasserstein analysis bounds the unweighted proposal's terminal error using this residual. These results motivate Risk-Calibrated Proposal Transport (RCPT), which uses deletion leave-one-out residuals to calibrate the retained fraction of the VCG update, adding no model calls and only small linear-algebra overhead. Experiments on 2D checker distributions, scaffold decoration, molecular property optimization, and class-conditional CIFAR-10 generation demonstrate recovery from harmful fitted updates. Across molecular and image domains, RCPT mitigates harmful fitted updates and improves a broad range of terminal metrics relative to uncalibrated VCG.

stat.ML↗

arXiv2026

SurfSpec: Enhancing Off-Target-Agnostic Specificity by Bounding Pocket-Ligand Geometric Mismatch

Lead optimization in structure-based drug design aims to improve target binding while avoiding unintended interactions with off-target pockets. However, existing affinity-driven methods do not explicitly control specificity, whereas current specificity-aware approaches commonly require prior knowledge of off-target structures. We address off-target-agnostic specificity-aware lead optimization by analyzing the geometric mismatch between a ligand and the target pocket. We provide a conservative specificity lower bound for geometrically separated off-targets without requiring access to off-target structures. By metricizing pocket--ligand mismatch, the triangle inequality shows that reducing target--ligand mismatch improves a conservative lower bound on mismatch to a separated off-target class, which can be translated into a specificity lower bound through an empirical geometry--affinity calibration. Motivated by this analysis, we introduce SurfSpec, an off-target-agnostic lead optimization framework that iteratively grows ligands toward under-occupied regions of the target pocket surface. SurfSpec alternates between linker generation toward selected target-surface patches, which provides geometric pseudo-labels, and refinement under a pocket-conditioned ligand prior, which restores these pseudo-labels into valid ligands. On the CrossDocked2020 test set, SurfSpec reduces geometric mismatch and outperforms evaluated off-target-agnostic lead optimization baselines in empirical specificity, while maintaining competitive target-affinity improvement.

q-bio.QM↗

arXiv2026

ISAC: Training-Free Instance-to-Semantic Attention Control for Multi-Instance Generation

Recent open-weight text-to-image (T2I) diffusion models still struggle with multi-instance prompts, often omitting or merging instances and mixing semantics among similar objects. We trace these failures to early denoising steps, before instance boundaries are reliably stabilized. Existing training-free guidance is largely driven by cross-attention or other token-conditioned semantic signals. Such guidance can separate concepts at the token level, but largely assumes that distinct instance regions have already emerged. In early denoising steps, it cannot reliably carve out these regions, so count failures and semantic mixing persist. By contrast, self-attention exposes class-agnostic instance layouts during early denoising. To exploit this asymmetry, we propose $\textbf{ISAC}$ ($\textbf{I}$nstance-to-$\textbf{S}$emantic $\textbf{A}$ttention $\textbf{C}$ontrol), a training-free, model-agnostic objective that first stabilizes self-attention layouts and then binds cross-attention semantics within them, without fine-tuning or external vision models. Across T2I-CompBench, HRS-Bench, and our newly curated IntraCompBench, ISAC consistently outperforms prior training-free methods. Furthermore, ISAC enhances layout-to-image controllers by refining coarse, overlapping bounding boxes into dense instance masks. Code and IntraCompBench are available at https://shjo-april.github.io/ISAC.

cs.CV↗

arXiv2026

On the Collapse of Generative Paths: A Criterion and Correction for Diffusion Steering

Inference-time steering adapts pretrained diffusion and flow models to new tasks without retraining, often utilizing ratio-of-densities constructions that reweight time-indexed marginals with fixed exponents. We identify Marginal Path Collapse, a failure mode in which the intermediate density defined by such compositions becomes non-normalizable despite valid endpoints. This collapse can arise when composing heterogeneous experts trained with mismatched noise schedules (and/or negative exponents / partial supports). To address this, we provide (i) a sharp sufficient Path Existence Criterion that characterizes when the composed intermediate densities are mathematically well-defined, and (ii) Adaptive Path Correction with Exponents (ACE), which generalizes Feynman-Kac steering to support time-varying exponents. Our analysis reveals that ACE controls the quantile radius of the intermediate distributions, providing a theoretical mechanism for path stabilization observed in experiments. On flexible-pose scaffold decoration, a drug design task composed of de-novo, conformer, and protein-conditioned experts, ACE prevents collapse and significantly outperforms constant-exponent baselines. Furthermore, ACE improves attribute success rates in compositional image generation, establishing it as a general framework for compositional sampling. Project Page: https://ziseoklee.github.io/projects/ACE/

cs.AI↗

arXiv2026

TRACE: Your Diffusion Model is Secretly an Instance Edge Detector

High-quality instance and panoptic segmentation has traditionally relied on dense instance-level annotations such as masks, boxes, or points, which are costly, inconsistent, and difficult to scale. Unsupervised and weakly-supervised approaches reduce this burden but remain constrained by semantic backbone constraints and human bias, often producing merged or fragmented outputs. We present TRACE (TRAnsforming diffusion Cues to instance Edges), showing that text-to-image diffusion models secretly function as instance edge annotators. TRACE identifies the Instance Emergence Point (IEP) where object boundaries first appear in self-attention maps, extracts boundaries through Attention Boundary Divergence (ABDiv), and distills them into a lightweight one-step edge decoder. This design removes the need for per-image diffusion inversion, achieving 81x faster inference while producing sharper and more connected boundaries. On the COCO benchmark, TRACE improves unsupervised instance segmentation by +5.1 AP, and in tag-supervised panoptic segmentation it outperforms point-supervised baselines by +1.7 PQ without using any instance-level labels. These results reveal that diffusion models encode hidden instance boundary priors, and that decoding these signals offers a practical and scalable alternative to costly manual annotation. Project Page: https://shjo-april.github.io/TRACE/

cs.CV↗