arXiv subjects

Mingquan Liu

Publications and source records attributed to Mingquan Liu.

5 recordsLinked to original sources

arXiv2026

AgentFold: Closed-Loop Agentic Search for Protein Folding Model Design

Scientific LLM agents have shown promise in literature reasoning, tool use, and experiment planning, but it remains unclear whether they can autonomously improve large, tightly coupled scientific machine-learning systems through executable code changes and computationally expensive validation. We study this question in protein folding, where progress requires coordinated architectural modifications, multi-objective evaluation, and domain-aware interpretation. We present AgentFold, a multi-agent framework that formulates folding-model development as a closed-loop search over executable code variants. Starting from ESMFold, AgentFold proposes hypotheses, implements and debugs code-level modifications, evaluates model variants, analyzes experimental outcomes, and stores both successful and failed interventions in structured memory. An MCTS-style policy allocates computational resources across high-scoring search branches. On an engineering-scale protein-folding codebase comprising more than 2,000 lines of code, AgentFold explores approximately 80 model variants using approximately 5,000 GPU-hours and 170 million LLM tokens. Under a matched computational budget, AgentFold improves the best lDDT by 7.5% over independent Codex proposals and outperforms a random-search control. Beyond model improvement, the resulting intervention traces reveal recurring empirical design patterns: stable gains tend to arise from early, soft, learnable priors and gated refinement, whereas direct geometric perturbations and geometry-conditioned feedback often destabilize training. The code and experimental resources are publicly available at https://github.com/lmqfly/AgentFold.

cs.AI↗

arXiv2026

An accurate nucleic acid-small molecule docking framework via geometric deep learning with large-scale pretraining

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. Physics-based docking methods often show limited accuracy and efficiency, whereas deep learning approaches are constrained by the scarcity of experimentally resolved nucleic acid-ligand complexes. Here, we present NucleoDock, a deep learning framework for nucleic acid-small molecule docking. To address data scarcity, NucleoDock combines physics-guided large-scale pretraining on millions of docking-generated synthetic complexes with fine-tuning on curated experimental co-crystal structures. It further integrates sequence- and structure-informed nucleotide representations with atomistic three-dimensional features to capture both biological context and binding-site geometry. A mixture density network-based geometric scoring head is used to model conditional interaction-distance distributions for pose ranking. On an external benchmark of 125 nucleic acid-ligand complexes, NucleoDock achieved a top-1 success rate of 56 percent at an RMSD cutoff of 2.0 Angstrom, outperforming rDock with 29 percent, while generating 100 poses in approximately 5 seconds per complex. Retrospective virtual screening on the ROBIN benchmark further showed improved early enrichment. NucleoDock represents a step toward bridging the methodological gap between protein- and nucleic acid-directed computational drug discovery.

q-bio.BM↗

arXiv2026

Nexusformer: Nonlinear Attention Expansion for Stable and Inheritable Transformer Scaling

Scaling Transformers typically necessitates training larger models from scratch, as standard architectures struggle to expand without discarding learned representations. We identify the primary bottleneck in the attention mechanism's linear projections, which strictly confine feature extraction to fixed-dimensional subspaces, limiting both expressivity and incremental capacity. To address this, we introduce Nexusformer, which replaces linear $Q/K/V$ projections with a Nexus-Rank layer, a three-stage nonlinear mapping driven by dual activations in progressively higher dimensional spaces. This design overcomes the linearity constraint and enables lossless structured growth: new capacity can be injected along two axes via zero-initialized blocks that preserve pretrained knowledge. Experiments on language modeling and reasoning benchmarks demonstrate that Nexusformer matches Tokenformer's perplexity using up to 41.5\% less training compute during progressive scaling (240M to 440M). Furthermore, our analysis of growth dynamics reveals that zero initialization induces a stable convergence trajectory, allowing us to derive a geometric scaling law that accurately predicts performance across expansion scales.

cs.LG↗

arXiv2025

EDBench: Large-Scale Electron Density Data for Molecular Modeling

Existing molecular machine learning force fields (MLFFs) generally focus on the learning of atoms, molecules, and simple quantum chemical properties (such as energy and force), but ignore the importance of electron density (ED) $ρ(r)$ in accurately understanding molecular force fields (MFFs). ED describes the probability of finding electrons at specific locations around atoms or molecules, which uniquely determines all ground state properties (such as energy, molecular structure, etc.) of interactive multi-particle systems according to the Hohenberg-Kohn theorem. However, the calculation of ED relies on the time-consuming first-principles density functional theory (DFT) which leads to the lack of large-scale ED data and limits its application in MLFFs. In this paper, we introduce EDBench, a large-scale, high-quality dataset of ED designed to advance learning-based research at the electronic scale. Built upon the PCQM4Mv2, EDBench provides accurate ED data, covering 3.3 million molecules. To comprehensively evaluate the ability of models to understand and utilize electronic information, we design a suite of ED-centric benchmark tasks spanning prediction, retrieval, and generation. Our evaluation on several state-of-the-art methods demonstrates that learning from EDBench is not only feasible but also achieves high accuracy. Moreover, we show that learning-based method can efficiently calculate ED with comparable precision while significantly reducing the computational cost relative to traditional DFT calculations. All data and benchmarks from EDBench will be freely available, laying a robust foundation for ED-driven drug discovery and materials science.

physics.chem-ph↗

arXiv2025

RAUM-Net: Regional Attention and Uncertainty-aware Mamba Network

Fine Grained Visual Categorization (FGVC) remains a challenging task in computer vision due to subtle inter class differences and fragile feature representations. Existing methods struggle in fine grained scenarios, especially when labeled data is scarce. We propose a semi supervised method combining Mamba based feature modeling, region attention, and Bayesian uncertainty. Our approach enhances local to global feature modeling while focusing on key areas during learning. Bayesian inference selects high quality pseudo labels for stability. Experiments show strong performance on FGVC benchmarks with occlusions, demonstrating robustness when labeled data is limited. Code is available at https://github.com/wxqnl/RAUM Net.

cs.CV↗