AdaptNTK: Adaptive Uncertainty Quantification and Active Learning for Neural Network Potentials

Machine learning interatomic potentials bridge the gap between quantum chemical precision and classical computational speed, enabling molecular dynamics simulations with first-principles accuracy. Their reliability is often improved through active learning, which iteratively expands the training set by identifying uncertain, out-of-distribution configurations. Existing uncertainty-quantification methods often involve a trade-off between computational cost and reliability, and generally cannot account for redundancy as an acquisition batch is assembled. Here, we introduce AdaptNTK, a single-model framework that measures uncertainty as a regularized Mahalanobis distance in empirical neural tangent kernel (NTK) feature space. With the NTK features fixed during acquisition, the uncertainty depends on the acquired configurations but not their reference labels. This allows the uncertainty to be updated recursively after each selection without retraining, reducing redundancy within an acquisition batch. On held-out rMD17 data, AdaptNTK achieves the highest mean correlations with force errors (Spearman 0.68, Pearson 0.71) and matches a three-member ensemble in error retention. In active learning experiments, AdaptNTK achieves the lowest force errors across rMD17 and Transition-1X, with particularly strong performance on transition-state configurations in Transition-1X. AdaptNTK provides a 2.6-fold speedup per Transition-1X cycle relative to the ensemble, providing efficient single-model uncertainty estimation with sequential updates for data-efficient active learning.

Cross-Temperature Defect Identification in Atomistic Simulations via Multi-Level Domain Alignment

Identifying atomic defects at elevated temperature is difficult because thermal fluctuations blur the local symmetry that both geometric heuristics and supervised classifiers rely on: trustworthy labels exist in low-temperature reference configurations, while the high-temperature regime where robust analysis matters most is effectively unlabeled. We cast this as a cross-temperature domain-shift problem and align the two domains at three levels: an equivariant denoiser at the input level, cross-temperature contrastive learning at the representation level, and a morphology-aware regularizer that steers predictions toward the compact geometry of physical defect structures. Because no atom-wise truth exists at temperature, we further introduce a label-free evaluation suite that scores predicted defect structures along five spatial and physics-based axes, enabling model assessment and selection without high-temperature labels. Near the melting point, the framework identifies vacancies and self-interstitial atoms across face-centered-cubic, body-centered-cubic, and hexagonal-close-packed iron systems with every interstitial localized and zero false detections in every vacancy system against Wigner-Seitz ground truth, with no high-temperature labels used in training. It sustains this fidelity on a million-atom, 2.5 ns trajectory, resolving single vacancy hops and complete Frenkel-pair recombination, and captures grain-boundary phase transformations in aluminum bicrystals, distinguishing two nucleation modes. Multi-level domain alignment thus offers a practical, label-efficient route to temperature-robust structural analysis of large-scale molecular dynamics.

First-Principles Atomistic Structure and Dynamics of Polyethylene During High-Pressure Radical Polymerization via Machine Learning Force Fields

Polyethylene (PE) is one of the most commonly used synthetic polymers. While the synthesis and processing protocols for PE are well established, precise experimental assignment of microscopic structures at atomistic resolution (i.e., the position of each atom) remains largely limited to highly crystalline systems. This gap is often addressed via computer simulations using empirical interatomic potentials, which use approximate but efficient descriptions of interatomic interactions to reach the length and time scales needed to describe macromolecules. These empirical potentials typically perform well for bulk and/or collective properties but face challenges with chemical realism for complex systems, e.g., during reactive processes. In this work, we address this challenge by combining the computational efficiency of a deep potential (DP) machine-learning force field and the chemical realism of first-principles van der Waals (vdW) corrected hybrid density functional theory (DFT) enabled by a SeA high-throughput framework. Using this approach, we study the structure and dynamics of PE oligomers and polymers in an ethylene solvent under common high-pressure (supercritical) radical polymerization conditions. We found that the local solvation environment of radical-containing PE oligomers converges for chain lengths greater than (n~6), suggesting extensibility of our oligomer-trained MLFF to significantly longer polymers. We then confirmed the extensibility of these models to long PE chains by characterizing the molecular weight scaling of single-chain structure and dynamics, which showed classic good solvent behavior. Our PE MLFF retained a consistent level of fidelity and stability across a wide range of thermodynamic state points and chain lengths, at full atomistic resolution, therefore paving the way towards first-principles-based polymer structure and property prediction.

Stochastic Control Policies for Robust Molecular Transition Path Sampling

Transition path sampling (TPS) aims to efficiently generate rare molecular transition trajectories between metastable states and is essential for understanding biomolecular mechanisms. Beyond traditional molecular dynamics (MD)-based sampling, machine learning has become central to state-of-the-art TPS. One major class of methods learns control forces during explicit MD rollouts. By preserving the underlying molecular dynamics, these methods tend to produce more physically plausible trajectories than endpoint-conditioned generators that construct paths directly. However, rollout-based control methods have been reported to exhibit unstable and strongly seed-dependent performance. We recast rollout-based control as learning a path-space proposal distribution and investigate stochasticity placement as a design choice for improving exploration and optimization robustness. We develop two stochastic policies: FS-TPS, which directly parameterizes a state-dependent Gaussian distribution over the control policy output, and LaS-TPS, which samples a compact latent control variable and decodes it into structured, cross-atom-correlated force variation. We conduct extensive multi-seed experiments on three biomolecular systems of increasing size: alanine dipeptide, chignolin, and BBL, a fast-folding protein. Stochastic policies consistently improve transition success and path quality over deterministic-policy baselines while substantially reducing sensitivity to random initialization.

DynaPPI: A Large-scale Dynamic Protein Dataset for AI-driven Advances in Protein Interactomics

Diffusion models have been widely explored in protein backbone generation due to their powerful generation capabilities.However, in today's AI-driven biological research, predicting the structure of unknown multi-chain protein aggregates (called "complexes" in biology) remains an unsolved challenge.This is because existing static or dynamic protein datasets focus solely on static snapshots or single-entity trajectories, neglecting the dynamic process of multiple monomers forming complexes.To alleviate this dilemma, we present DynaPPI, a dynamic protein dataset comprising molecular dynamics (MD) trajectories of protein complex formation from dissociated chains to the bound state, as a pivotal resource to bridge the gap between static structural biology and the inherently temporal nature of dynamic molecular interactions.Benefiting from this dataset, diffusion models can explicitly learn the dynamic binding trajectories of known complexes and accurately predict the structures of unknown complexes based on their diverse generative properties, thereby further catalyzing AI-driven structural biology and protein interactomics.

Temperature-Driven Sequential Modeling for the Prediction of Annual Power Conversion Efficiency Profiles of Organic Photovoltaic Materials: Douala Case Study

Organic photovoltaic (OPV) materials are promising candidates for distributed solar energy in tropical regions, yet existing virtual screening tools report static power conversion efficiency (PCE) values at standard testing conditions (STC) that fail to capture the temperature-driven performance degradation experienced under real deployment conditions. Here we introduce a Climate-Native computational framework that forecasts the annual PCE profile of OPV donor molecules under geographically realistic operating conditions. The framework combines GFN2-xTB molecular dynamics with an equivariant graph neural network surrogate ($268$ Neyman-stratified CEP molecules; $120,600$ training geometries; $\sim 1050\times$ speedup over explicit quantum chemistry) and sequential deep learning models trained on annual time series anchored in NASA POWER climate data for Douala, Cameroon, and validated by zero-shot transfer to Yaoundé and Maroua. Applied to $\sim 30,000$ molecules from the Harvard Clean Energy Project (CEP) and validated against $350$ HOPV15 experimental device measurements, the framework demonstrates that sequential models trained on full molecular dynamics trajectories outperform time-averaged baselines ($35\%$-$48\%$ relative MAE improvement over static baselines), confirming that thermal conformational dynamics carry information beyond mean geometry. We further introduce a seasonal stability score that reranks OPV candidates by performance consistency under tropical conditions, identifying molecules whose deployment suitability differs substantially from their static PCE ranking.

A Multi-Agent Framework for Automated Coarse-Grained Molecular Dynamics of Polymers

Coarse-grained (CG) molecular dynamics extends polymer simulation beyond the scales accessible to all-atom (AA) methods, but bottom-up CG modeling is laborious. The CG resolution is a design choice, so a transferable parameter set is generally not available and the potentials are derived anew for each polymer mapping. Here we present CGMas, a multi-agent framework that automates topology construction, equilibration, mapping, potential derivation, and validation from a natural-language specification of the polymer and target resolution. A large-language-model (LLM) reasoning agent infers the AA topology from polymer name, while layered self-correction resolves physical errors common to unsaturated, heteroatom-containing, and polar polymers. Downstream agents equilibrate the system, map it onto CG representation, derive potentials through Boltzmann inversion, and benchmark the model against its atomistic reference. CGMas completed all 27 homopolymer and copolymer tasks, matched the AA density to within 5% in 22, and reduced simulation from 38-88 min to 1 min, establishing agentic LLMs as a route to automated polymer coarse-graining.

MDArena: Evaluating Coding Agents on Realistic Molecular Dynamics Workflows

Accelerating scientific discovery is among the most consequential applications of AI, and computational biomolecular simulation stands out as a particularly promising target within this broader effort. Coding agents promise to automate significant portions of this workflow, yet their reliability on realistic molecular dynamics (MD) tasks remains poorly characterized. To address this issue, we introduce MDArena, a benchmark of 50 containerized tasks drawn from active biomolecular simulation projects, spanning 29 molecular systems and 14 broad research protocols, including trajectory analysis, complex system preparation, free-energy protocols, and enhanced sampling. We evaluate six model/harness configurations spanning Codex and OpenCode. Among the evaluated configurations, Codex GPT-5.5 at extra-high reasoning effort performs best, reaching 24/50 Strict-Pass@1 successes (48%), followed by Codex GPT-5.5 Medium with 21/50, and OpenCode Gemini Flash 3.5 with 20/50. Average correctness and process rewards are substantially higher than strict success rates across all configurations, indicating that agents frequently make meaningful partial progress but fail on the fine-grained details required for reproducible scientific workflows. Hard tasks remain largely unsolved, particularly membrane-protein system preparation and alchemical free-energy setup, both unsolved or near-unsolved by every evaluated configuration. MDArena thus exposes a substantial gap between the usefulness of coding agents as supervised assistants and their reliability as autonomous MD researchers, while providing a reproducible and extensible platform for tracking progress toward closing it.

Implicit Machine Learning Force Fields Accelerate Molecular Dynamics Simulations

We introduce implicit machine learning force fields (I-MLFFs), which replace explicit stacks of neural network layers with self-consistent fixed-point equations. In molecular simulations, this formulation enables intermediate representations to be reused across successive timesteps, thereby warm-starting force evaluation. The resulting models effectively combine the computational footprint of a shallow, single-layer MLFF with the representational capacity and accuracy of a deep neural network. Our approach unlocks architecture-agnostic efficiency gains that are inaccessible when force prediction and trajectory integration are considered separately. We demonstrate this across three major classes of graph neural networks: invariant, equivariant Cartesian tensor, and SO(3)-equivariant spherical-tensor architectures. Each yields a two- to five-fold reduction in compute and memory footprint. Crucially, these gains are achieved while retaining full atomistic resolution and the original integration timestep, avoiding spatial or temporal coarse graining. Our contribution therefore advances the scaling frontier of quantum-mechanically faithful molecular simulation, enabling longer trajectories and larger atomistic systems within fixed GPU memory and compute budgets, and thereby opening access to new insights across biomolecular and material systems.

Graph Neural Network Force Fields for Spin Dynamics in Metallic Magnets

Metallic magnets exhibit complex spin dynamics governed by electronically generated interactions. Predictive simulations of such dynamics typically require repeated solutions of an underlying electronic problem throughout the time evolution, creating a major computational bottleneck. Here we introduce a graph neural network (GNN) magnetic force-field framework that learns the effective magnetic energy functional governing itinerant spin dynamics directly from electronic calculations. Conceptually analogous to machine-learned interatomic potentials, the proposed framework enables efficient evaluation of spin torques while capturing the nonlinear and spatially extended interactions generated by itinerant electrons. We benchmark the method on representative metallic magnetic systems exhibiting collinear, noncollinear, and noncoplanar magnetic order. The learned force fields accurately reproduce electronically generated spin torques and yield nonequilibrium spin dynamics in excellent agreement with direct electronic simulations. Our results establish graph neural networks as a powerful framework for machine-learned magnetic force fields, providing a pathway toward predictive large-scale simulations of nonequilibrium magnetism across multiple length and time scales.

Graph-Theoretic Neural Network Fragmentation with Covariant Direct Molecular Force Learning: Enabling Coupled-Cluster Accuracy AIMD for Fluxional Systems

Accurate ab initio molecular dynamics (AIMD) simulations of complex, fluxional chemical systems are severely limited by the high computational scaling of correlated electronic structure methods. To overcome this bottleneck, we present a robust, graph-theoretic molecular fragmentation framework integrated with machine learning to directly model post-Hartree-Fock nuclear forces at coupled cluster accuracy. Bypassing the limitations of automatic differentiation on learned energy surfaces that may struggle with link-atom Jacobians, our approach directly predicts nuclear force vectors. By projecting these vectors onto fragment-fixed principal axes of inertia, we establish co-variant descriptors that naturally preserve rotational, translational, and permutational invariance. The methodology achieves exceptional high parameter efficiency through a vector-valued training protocol that reduces trainable parameters by over an order of magnitude, while an unsupervised mini-batch k-means space tessellation algorithm constructs highly representative training databases using only 10% to 20% of reference configurations. We rigorously validated this framework on the highly fluxional solvated Zundel cation H_{13}O_6^+ ). Our fully machine-learning-predicted AIMD trajectories successfully reproduced complex dynamical signatures and key structural characteristics, including radial distribution functions and the velocity autocorrelation power spectrum. Ultimately, this scalable, systematically improvable framework bridges the gap between high-level correlated wavefunction theories and long-timescale reactive sampling, laying the foundation for advanced, LLM-inspired transfer learning in modern chemical dynamics simulations.

DyneTrion: A Spatio-temporally Coherent Generative Emulator for Protein Dynamics Across Timescales

Proteins function through coordinated motion across multiple spatial and temporal scales, underpinning processes such as ligand binding, allostery, and catalysis. However, accessing long-timescale conformational change through molecular dynamics (MD) simulations remains prohibitively expensive for systematic exploration across diverse systems. Here, we present DyneTrion, a generative protein dynamics emulator that jointly enforces geometric symmetry, structural consistency and temporal coherence within a single framework. DyneTrion uses a tri-attention architecture that integrates invariant point attention (IPA) for SE(3)-robust geometric updates, spatial attention anchored to a reference conformation to preserve structural integrity, and temporal attention to model correlated evolution across time frames. Across 100-ns MD trajectory simulation benchmarks, DyneTrion reproduces MD-derived flexibility, ensemble distributions and interaction observables while maintaining stereochemical validity during extrapolation. To evaluate long time-scale generalization, we introduce dynamicPDB, a dataset of over 10,000 proteins with up to 1-$μ$s all-atom trajectories at 10-ps resolution and accompanying physical annotations. On microsecond trajectories, DyneTrion preserves free-energy landscapes and metastable-state populations, and it supports large conformational propagation in apo-to-holo transitions and fast folders. Together, DyneTrion provides a scalable path from static structure prediction toward time-resolved, ensemble-faithful protein modeling. The code is publicly available at https://github.com/fudan-generative-vision/DyneTrion

Transferable Implicit Solvent Machine Learning Potential for Drugs and Proteins Approaching Ab Initio Accuracy

Machine learning interatomic potentials (MLPs) have revolutionized atomistic modeling, offering the potential to replace traditional methods like Density Functional Theory (DFT). However, inference time of MLPs is orders of magnitude slower than that of classical force fields, hindering real-world applications for biomolecular systems that require timescales of microseconds and beyond. Implicit solvent MLPs can address this issue, but are faced with data challenges associated with coarse-grained modeling. Consequently, previous approaches relied on empirical force field data, thereby inherently limiting the MLP's accuracy. Here, we introduce the Transferable Water Implicit Network (TWIN), an implicit water MLP parametrized entirely by an Equivariant Graph Neural Network and trained solely on ab initio and experimental labels. We demonstrate TWIN's transferability across drug-like molecules, peptides, and proteins, achieving excellent results on ab initio and experimental crystallographic and NMR benchmarks, consistently outperforming previous machine-learning-based implicit solvent or coarse-grained models. Furthermore, TWIN closely matches DFT-based explicit solvent MLPs while providing a two-order-of-magnitude faster timestep evaluation, paving the way for efficient ab initio-level modeling of biomolecular systems in aqueous environments.

Active rejection enables reliable generalization of universal machine-learning interatomic potentials

Universal machine learning interatomic potentials (uMLIPs) bridge quantum-mechanical accuracy and large-scale molecular dynamics, but the cost of high-accuracy calculations such as r$^2$SCAN limits training to datasets that remain small relative to the open materials space. Strong average benchmark performance also does not guarantee reliable energy--force predictions for every structure. We propose Adaptive Multi-Teacher Routing (ATR), which reformulates high-fidelity data construction as a structure-wise decision problem under uncertainty. Using a small set of real r$^2$SCAN labels, ATR calibrates multiple pretrained uMLIP teachers and combines structural descriptors, teacher identity, and inter-teacher disagreement to estimate the reliability of each structure--teacher pair. It selects high-confidence predictions for pseudo-label generation and rejects structures for which no teacher is sufficiently reliable. With real r$^2$SCAN labels for only 0.2\% of candidate structures, ATR distils 2.89 million traceable r$^2$SCAN-level pseudo-labels for pretraining. On held-out r$^2$SCAN structures and the MP-r$^2$SCAN benchmark, a lightweight CHGNet trained on the ATR-generated dataset consistently outperforms the baseline and non-routed controls. Finite-temperature molecular dynamics further shows that ATR improves dynamical robustness across multiple material systems, maintaining stable trajectories where baseline simulations undergo catastrophic structural collapse. These results establish active rejection as an effective mechanism for converting multiple pretrained uMLIPs into a scalable and reliable data-construction system for high-fidelity uMLIPs.

EquiFiLM: Charge-Conditioned Equivariant Force Fields via Feature-wise Linear Modulation

Foundation machine learning force fields (MLFFs) such as MACE-MP-0 and UMA cover broad chemical space at near density functional theory (DFT) accuracy. However, they assume equilibrium ground-state physics and do not natively handle externally induced changes to the electronic state, such as charging, applied fields, or electronic excitation, which limits their use for driven processes such as photoexcitation and charge injection. We propose EquiFiLM, a lightweight extension that adds continuous external conditioning to any equivariant foundation MLFF via a per-layer Feature-wise Linear Modulation (FiLM) block, learning externally driven changes to the potential energy surface from minimal training data. The block modulates only scalar channels and preserves E(3)-equivariance exactly. We demonstrate the recipe on charged liquid water with the foundation model MACE-MatPES as the backbone, yielding E-MACE. On the four training charges, E-MACE delivers a $3.1\times$ reduction in force RMSE ($21.3$ to $6.96$ meV/$\mathring{A}$) and a $61\times$ reduction in per-atom energy RMSE ($6.1$ to $0.1$ meV/atom) over a baseline without EquiFiLM trained on the same data, at indistinguishable inference cost. Across seven held-out interpolation and extrapolation charges, force RMSE stays within $18-61$ meV/$\mathring{A}$ and energy RMSE within $0.7-5.4$ meV/atom. The model runs stable molecular dynamics across the full range tested and predicts the charge-dependent first-shell response of the reduced pair distribution function probed by ultrafast electron diffraction. Adding this conditioning axis to the foundation requires only a few thousand DFT-labeled frames, against the $\approx 10^8$ structures of a charge-aware foundation trained from scratch. The recipe is backbone- and conditioning-agnostic: it applies without architectural change to any equivariant MLFF with scalar interaction-layer channels.

Physically-Relevant Information Learning in High-Dimensional Time-Derivatives Spaces

Understanding the physics of many-body complex dynamical systems is typically non-trivial. High-dimensional analysis approaches are often deemed necessary to prevent losing important information. Typically, these use order parameters or descriptors capturing information related to, e.g., relative positions, symmetries, etc., of the units in the studied system. However, in many cases, gaining information related to the relative positions (or velocities) of the constitutive units alone may be insufficient, and to reach a more complete physical knowledge, one should ideally learn and correlate with each other both structure and dynamics. Here we demonstrate how to efficiently achieve such a goal by building and navigating high-dimensional Time-Derivatives (TiDe) space. A TiDe space can be easily generated for virtually any type of system/phenomenon under study from the time-series data collected along its observation over time. Each TiDe's dimension corresponds to a growing-order time-derivative of the extracted data, thus containing information related to different types of physical phenomena/events that can be easily extracted via unsupervised approaches. We demonstrate how, by definition, TiDes can be directly analyzed without a need for prior dimensionality reduction, providing results that are intrinsically intuitive to interpret. We show the potential of the method by analyzing two prototypical example datasets extracted from molecular dynamics simulations or experimental tracking of different complex dynamical systems. Our results demonstrate how efficiently one can navigate and learn in such information-rich TiDe spaces, which provide robust general frameworks for data analysis and for studying complex dynamical systems from the data collected along their observation over time.

AquaGen: Scaling generative models to molecular dynamics precision on thousands of atoms

We present AquaGen, the first all-atom, explicit solvent, periodic-boundary-condition-aware generative model that produces molecular configurations from the Boltzmann distribution at a fraction of the cost of molecular dynamics (MD). This is in contrast with existing generative models that remove degrees of freedom by operating on coarse-grained, vacuum, or implicit solvent systems. Operating at this resolution allows for post-processing through force field energy evaluations and MD simulations, and enables the prediction of relevant properties in a gray-box manner (as ensemble averages of potential energy evaluations over generated samples). We demonstrate the utility of this paradigm on absolute hydration free energy (AHFE), producing estimates 4-10x faster and with comparable accuracy to standard GPU-based MD. By generating uncorrelated samples from alchemical Boltzmann distributions, we create more accurate, interpretable, and refinable ensemble predictions with calibrated uncertainty estimates, unlike regression methods which are entirely black-box predictors. Our approach also yields predictable benefits from increasing train- and test-time compute, realized by scaling model size and generating more samples, respectively. We believe that this approach demonstrates the utility of high-resolution ensemble generation for free energy estimation, with future potential to replace MD in tasks such as the prediction of lipophilicity, membrane permeability, or absolute binding free energy (ABFE) -- whose grounding and interpretability may be critical for the development of new drugs and materials.

Geometric Algebra Meets Cartesian Tensors: Higher-Order Equivariance for Interatomic Potentials

$\mathrm{Cl}(3,0)$ interatomic potentials, despite their algebraic elegance, predict force magnitudes accurately but force directions poorly. Across ten rMD17 molecules, every $L \leq 1$ baseline in our twelve-model study attains aggregate force-cosine similarity below $0.25$. The cause is structural. The geometric product of two vectors in $\mathbb{R}^3$ realises only the $L=0$ and $L=1$ components of its irreducible representation content, leaving the symmetric-traceless rank-2 component absent from the per-edge bilinear that drives each message-passing layer. We address this with CliffordSTF, which couples the Clifford multivector to closed-form symmetric-traceless tensor tracks at ranks two and three through bilinear cross-track contractions, using a single learned bilinear and no Clebsch--Gordan tables, Wigner-$D$ matrices, or e3nn calls. On rMD17, CliffordSTF raises aggregate force-cosine similarity from $0.055$ (base Clifford) to $0.551$, an order-of-magnitude relative directional gain, alongside improved magnitude accuracy (force MAE $15.8\%$ lower; energy MAE $10.9\%$ lower). It outperforms all CG-free or body-ordered baselines in our study (all $\leq 0.17$). On catalysis benchmarks, CliffordSTF achieves the best out-of-distribution S2EF energy MAE on OC22 in our experiments, and the best in-distribution energy MAE among $L \geq 2$ methods on OC22 IS2RE. An eleven-variant ablation shows the two tracks are complementary: neither alone matches the combined model.

ASTEROID: A Spatiotemporal Information Transformer for Forecasting Multi-Step Time Series of Molecular Dynamics

Molecular dynamics (MD) simulation is computationally demanding, particularly for large-scale systems requiring long-term analysis. Accurate forecast of the outcomes of a MD simulation is not only an attractive scientific challenge but also has substantial practical value. In this work, we developed a data-driven framework, termed ASTEROID (Advanced Spatiotemporal TransformER fOr Inferring Dynamics), that can directly predict multi-step atomic coordinates, avoiding conventional iterative integration. For this purpose, our ASTEROID reformulates MD trajectories as high-dimensional spatiotemporal sequences and integrates the Spatiotemporal Information (STI) Transformation equation into a Transformer architecture. The core innovation of ASTEROID lies in its ability to model multiscale spatiotemporal dependencies. In particular, for spatial dependencies, a local-global self-attention mechanism captures both short- and long-range interactions. For temporal dependencies, an encoder-decoder structure integrates global context with autoregressive forecasting. ASTEROID was evaluated on several quantum-mechanics derived molecular datasets. Our results indicate that ASTEROID achieved not only a higher level of accuracy in multi-step prediction than existing methods on various benchmarks, but also significantly reduced computational cost of conventional MD simulation. Moreover, the model supports iterative multi-step forecasting over an extended time scale. This work establishes a robust and generalizable data-driven paradigm for accelerating MD simulations.

Scalar-pathway fidelity improves physical accuracy in short-range equivariant interatomic potentials

Accurate interatomic potentials enable molecular dynamics of materials, molecules, and interfaces beyond density-functional-theory length and time scales. Equivariant neural network potentials have improved the representation of local geometry. However, their deployable energy surfaces ultimately manifest through invariant scalar channels, whose aggregation and spectral resolution remain comparatively underexamined. Here we use Physics-Aware Neighborhood (PAN) pooling and Physics-Guided Spectral (PGS) mixers as controlled scalar-pathway probes: lightweight, symmetry-preserving modifications that act only on \(\ell=0\) channels while leaving the equivariant tensor backbone unchanged. Using MACE as a high-body-order mechanistic scaffold, PAN adds coordination-sensitive amplitude modulation, whereas PGS augments edge and readout scalar features with radial and tapered spectral bases. Across metallic Ag, covalent Si, a short-range ionic LiF/Li--F subset, and MD17/rMD17 molecules, this scalar-pathway correction reduces MACE force errors by 22--27\% and energy errors by 19--22\%; on systems with stress labels, stress errors decrease by 27--28\%, at approximately 5\% additional inference-FLOPs cost. Directionally consistent gains in Allegro and NequIP further indicate that the correction is portable across distinct short-range equivariant backbones, although effect sizes remain architecture-dependent. These results identify scalar-pathway fidelity as a practical design dimension for short-range equivariant interatomic potentials.

A Fixed-Point Neural Operator for Size- and Functional-Transferable Hamiltonian Prediction

Predicting the Kohn-Sham Hamiltonian with machine learning can accelerate density functional theory while retaining access to molecular orbitals, energy levels, and electronic-structure observables that energy-only surrogates cannot resolve. Yet element-wise agreement with the converged Hamiltonian, an implicit fixed point of the self-consistent field iteration, does not determine the occupied subspace that governs orbital energies and densities. Here we present HamEvo, a neural operator that learns the single-step self-consistent update and returns the converged Hamiltonian as its fixed point. HamEvo is pre-trained on intermediate self-consistent trajectories and calibrated at equilibrium with density-matrix supervision. Across benchmarks from MD17 to drug-like QMugs, HamEvo lowers Hamiltonian errors by 35-49% over direct-regression and deep-equilibrium baselines, and predicts QMugs HOMO and LUMO energies with mean absolute errors of 0.036 and 0.053 eV, near the 1 kcal/mol chemical-accuracy scale. Few-shot fine-tuning with only 20 reference conformations extends HamEvo to molecules of up to 122 atoms, well beyond the size range covered by pre-training. With thermal molecular-dynamics sampling, HamEvo captures temperature-dependent HOMO-LUMO gap renormalization beyond the harmonic approximation. Inference is up to 242 times faster than conventional DFT.

Temperature transferable Machine Learned Coarse Grained model for proteins

Coarse-grained (CG) molecular simulations offer an efficient alternative to atomistic molecular dynamics to study large and complex biological systems. The accuracy of CG simulations has been increased dramatically by the introduction of machine-learned coarse-grained (MLCG) models. However, these models are typically designed to be used at a single thermodynamic point, lack temperature transferability, and can not be used to predict temperature dependent quantities like the heat capacity. Here we introduce a thermodynamically informed, temperature-transferable MLCG framework for proteins that explicitly decomposes the CG potential of mean force (PMF) into its energetic and entropic components. The model architecture enforces an exact thermodynamic relation between the energetic and entropic components of the PMF and guarantees physically consistent extrapolation and interpolation across temperature regimes. We validate this framework on an extensive dataset spanning a total of 250 $μ$s of molecular dynamics simulations across five temperatures between 300 K and 400 K for the Chignolin protein, and demonstrate that it reproduces the temperature dependency of the reference atomistic free energy surfaces, correcting the temperature-unaware baselines. Furthermore, we show that it is possible to apply an inexpensive, post-hoc temperature-dependent correction that does not require retraining the MLCG potential, accurately recovering the atomistic heat capacity at different temperatures. Overall, this work provides a physically grounded pathway toward thermodynamically transferable MLCG simulations of complex biomolecular systems.

MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at https://github.com/Zehong-Wang/MDForge.

Reactive Flux Matching: Mechanism Discovery and Adaptive Sampling of Rare Events

Path sampling methods generate ensembles of reactive trajectories connecting metastable states, but extracting mechanistic insight from these data remains nontrivial. We introduce Flux Matching, a framework that learns two complementary objects directly from reactive trajectory data: a current velocity $u(z)$, whose streamlines trace the dominant reaction pathways, and a scalar potential $h(z)$, obtained from a weighted Helmholtz-Hodge decomposition of the reactive current, that serves as a data-driven reaction coordinate. Both minimize quadratic functionals over the reactive path ensemble, analogous to the flow matching loss in generative modeling, and require no knowledge of the underlying dynamics or stationary distribution. Unlike committor-based methods, $u$ and $h$ remain well-defined under projection onto non-Markovian collective variables, and their level sets in turn provide adaptive interfaces for improved sampling with enhanced sampling methods. Flux Matching is validated through the generation of current velocity trajectories and rate constant calculations on molecular systems.

Stein Kernelized Molecular Dynamics for Active Learning of Interatomic Potentials

Machine learning interatomic potentials (MLIPs) enable efficient and accurate atomistic simulations but depend critically on the quality and diversity of the training data. We introduce Stein kernelized molecular dynamics (SKMD), an enhanced sampling method that uses interacting particle dynamics to acquire informative training configurations for the active learning and fine-tuning of MLIPs. SKMD corresponds to a stochastic variant of Stein variational gradient descent that is adapted for molecular dynamics by incorporating asynchronous particle updates and a kernel of global atomic descriptors, which provides a symmetry-aware measure of configurational similarity. Unlike other enhanced samplers used in molecular dynamics, SKMD preserves the Boltzmann distribution as the asymptotic distribution of the dynamics. This property enforces a balance between the exploration of diverse configurations and attraction toward high-probability regions of the energy landscape. We further propose an approach to efficient online data acquisition using an adaptive stopping criterion that selects non-redundant training data over the course of simulation. We demonstrate SKMD for the active learning of a neural network model of the Müller-Brown potential and the fine-tuning of a MACE interatomic potential for alanine dipeptide. Compared to active learning baselines, our method achieves higher model accuracy in fewer training iterations with the same number of acquired training samples.

Learning Topological Representations for Molecular Dynamics

Molecular dynamics (MD) simulations generate trajectories in a high-dimensional configuration space whose analysis critically depends on molecular descriptors, typically handcrafted observables or learned kinetic embeddings. Designing descriptors that are both expressive and broadly applicable, however, remains challenging. We study persistent homology (PH) as a general-purpose representation for MD and introduce the masked Flood complex, a protein-tailored modification of a recently introduced simplicial complex construction that emphasizes inter-residue structure at low computational cost. Vectorized persistence diagrams then provide information-rich, geometry-aware summaries of protein conformations, which we evaluate on protein class prediction, frame-level observable regression, and Markov state model (MSM) estimation from learned low-dimensional coordinates in a single shared representation space. Results on the mdCATH dataset show that PH-based descriptors are competitive across tasks, with masked Flood PH yielding the most consistent overall performance. Further, when using topologically-informed MSMs as a drop-in replacement within the recent MarS-FM framework for generative modeling of protein conformations, we obtain consistently better ensemble statistics than MSMs based on physical observables. Finally, we explore the transferability of the generative model to qualitatively different, fast folding, proteins.

Speculative Sampling For Faster Molecular Dynamics

Molecular dynamics (MD) is a key tool for simulating the dynamical behavior of atomic systems. However, MD is inherently serial, which makes it difficult to increase single-system throughput with concurrent compute. To address this, we introduce Langevin Speculative Dynamics (LSD), a distributed and model-agnostic speculative sampler for accelerating MD without adding relative error. Inspired by speculative methods in language and diffusion modeling, LSD uses a draft model to propose fast simulation steps and verifies them in parallel with a slower target model, applying a transport map from the draft to the target distribution. We extend speculative sampling to second-order Langevin dynamics, derive the achievable speedup as a function of physical parameters, show that LSD generalizes across different systems and draft-target combinations with a 3-9x speedup, and confirm theoretically and empirically that LSD samples trajectories from its target model distribution.

Learning Implicit Bias in Generative Spaces for Accelerating Protein Dynamics Emulation

Generative emulators of protein dynamics produce plausible trajectories at a fraction of the cost of molecular dynamics, but they inherit their training distribution and tend to revisit known states rather than reach rare ones under long-horizon extrapolation. Inspired by classical enhanced sampling, we introduce an implicit, history-dependent bias in the generative space of a pretrained emulator. Specifically, a history-aware score estimator augments the frozen emulator with a distance-weighted bias that steers reverse-time sampling away from previously generated structures, regularized by an environment-support term. To preserve structural validity at long horizons, a score-based refinement step re-projects drifted samples onto the data manifold using the frozen emulator. Our experiments demonstrate that the method (i) raises diversity by $35\%$ on DynamicPDB-80; (ii) on $12$ zero-shot Fast-Folding proteins, the learned bias alone reaches the unbiased emulator's coverage up to ${\sim}15\times$ faster, and pairing it with refinement reaches the coverage up to ${\sim}37\times$ faster while covering ${\sim}3\times$ as many low-energy states. Code will be released soon.

CARD: Coarse-to-fine Autoregressive Modeling with Radix-based Decomposition for Transferable Free Energy Estimation

Estimating free energy differences quantifies thermodynamic preferences in molecular interactions, which is central to chemistry and drug discovery. Despite fruitful progress, existing methods still face key limitations: classical computational approaches remain prohibitively expensive due to their reliance on extensive molecular dynamics simulations, while deep learning-based methods are constrained by either less-expressive generative models or input dimensions tied to a specific system, resulting in negligible generalization. To address these challenges, we propose CARD, a generative framework that employs a novel radix-based decomposition to bijectively convert 3D coordinates into mixed discrete-continuous sequences, enabling coarse-to-fine autoregressive modeling with enhanced expressiveness. Notably, the model corresponds to a distribution with zero free energy, serving as a proposal for absolute free energy computation of arbitrary systems without relying on alchemical pathways. Experiments across diverse tasks demonstrate that CARD matches the accuracy of classical computational methods on unseen systems with diverse topologies, while achieving an approximately 40-fold speedup in inference.

Learning Structure, Energy, and Dynamics: A Survey of Artificial Intelligence for Protein Dynamics

Protein dynamics underlie many biological functions, yet remain difficult to characterize due to the high computational cost of molecular dynamics simulations and the scarcity of dynamic structural data. This survey reviews recent advances in artificial intelligence for protein dynamics from three perspectives: learning from structural ensembles and trajectories, learning from physical energy signals, and learning to accelerate molecular simulations. We summarize representative methods for conformation ensemble generation, trajectory generation, Boltzmann generators, physics-aware adaptation, machine learning potentials, coarse-grained modeling, and collective variable discovery. We further discuss available datasets and key open challenges, such as scalability, thermodynamic consistency, kinetic fidelity, and integration with experimental constraints.