Boltzmann Distributions

Studying the dynamical behavior of a system often depends on characterizing how it transitions between long-lived states. Because such transitions are rare, observing them usually requires specialized enhanced sampling techniques. Transition Path Sampling (TPS) is a well-established method for generating reactive trajectories, which is simple to implement and does not require the definition of a preconceived reaction coordinate. However, its efficiency is limited by its sequential nature and the resulting correlations between sampled paths. Previous work addressed this limitation by combining TPS with a sampling scheme based on conditioned Boltzmann Generators, a generative machine learning model capable of sampling a given target probability distribution. This approach produces uncorrelated transition paths but relies on an accurate reaction coordinate, which is rarely known in advance. Building on recent advances in committor learning, specifically on the Artificial Intelligence for Molecular Mechanism Discovery (AIMMD) method, in this work we introduce GenAIMMD, an iterative algorithm that actively and self-consistently learns the ideal reaction coordinate (the committor) and trains a conditioned Boltzmann Generator to sample from arbitrary bias windows along it. GenAIMMD thereby provides a correlation-free and fully parallelizable path sampling scheme that does not require prior knowledge of the system's transition mechanism. We apply GenAIMMD to a two-dimensional toy model and a higher-dimensional polymer system. In both cases, GenAIMMD succeeds in training the Boltzmann Generator and learning the committor. Benchmark results show a substantial increase in performance compared to standard TPS.

The test error of a model plotted against its number of parameters $d$ falls, peaks when the model can just fit the training data, and falls again, exhibiting the double descent phenomenon. We explain the phenomenon with statistical mechanics. The training trajectory of a stochastic gradient-based method is a particle wandering over the energy landscape of the training loss at an induced temperature $T$, and a run that has equilibrated visits every parameter vector of a given training loss equally often, the fundamental postulate of statistical mechanics, with probability given by the Boltzmann distribution. Because training starts at an initial point and has only finite time to diffuse, it carries an effective weight decay, which makes every parameter a quadratic degree of freedom. The equipartition theorem then distributes the energy among the $d$ degrees of freedom in shares of $T/2$, so at a fixed training loss adding parameters lowers the temperature and drives the Boltzmann distribution toward the stationary path. Finally, adding parameters can only lower the $L^2$ norm of the stationary path, so a solution sampled at fixed loss is less likely to be large with increasing $d$, effectively increasing weight regularization.

Deep neural networks exhibit regular macroscopic behavior despite highly nonlinear dynamics in vast parameter spaces. We develop a statistical-mechanical description of learning directly in function space, treating parameter configurations as microscopic realizations and functions with their dynamical operators as macroscopic variables. For mean-squared loss, the exact error dynamics are governed by the learning operator $M=JJ^\ast$. Combining the dynamical Boltzmann weight of the conditional stochastic dynamics with the parameter-space density of states, whose local curvature defines a statistical operator $B$, and integrating over local fluctuations yields $\Phi_{\mathrm{fluc}}(M;B)=\frac{\sigma_\xi^2}{2}\log\det(M^{-1}+B)+\mathrm{const}.$ At fixed spectrum, this term is rotationally stationary when $[M,B]=0$, is minimized by pairing large eigenvalues of $M$ with small eigenvalues of $B$, and generates a local restoring contribution against rotational mismatch. For ReLU-type function spaces under mild stable statistical conditions, $B=\sigma_\xi^2L^\ast\mathcal K L$, where $L$ measures coarse-grained second-order structure. Thus the low-$B$ sector corresponds, up to bounded anisotropy of $\mathcal K$, to low structural curvature, implying a preference for faster relaxation along smooth, data-adaptive directions. These results identify function space as a natural macroscopic level for studying stable collective organization in learning.

Normalizing flow Boltzmann generators retain a tractable pushforward density, but training with forward KL depends on target samples that may be biased or omit modes. As a result, a flow can miss target mass while its observed importance weights give a high effective sample size. We introduce the log-ratio variation $\X_ω$, the mean absolute pairwise difference of the target-to-pushforward log-density ratio under a weighting measure $ω$, and use it to define KLXX, a new loss function. Two log-ratio variations are added to the forward KL (denoted by the two X's): one weighted by the target to improve accuracy, the other by a mixture of quench and temper samples with pushforward samples to search candidate modes. We derive the Fisher--Rao gradient flow of KLXX, where both variations contribute nonpositive dissipation, and a fixed-surrogate error bound for KLXX. We use KLXX in an adaptive-staging Boltzmann generator, with importance reweighting at every stage. We bound the sampling error of its inference scheme when the stage weights are essentially bounded, and prove it asymptotically unbiased in the sample size. In the numerical tests, KLXX improves mode coverage over forward KL. It also improves the generator's per-stage diagnostics against the loss that built the schedule. The observables the generator recovers are close to independent references. The log-ratio variations thus supply information that the forward KL loss usually omits.

In this paper, we extend a weak adversary neural network pushforward method for solving time dependent Boltzmann equation and a weak formulation of the collision operator is proposed where an invertible neural pushforward mapping is used to generating samples given by the distribution governed by the Boltzmann equation. The training of the pushforward mapping is learnt by enforcing the weak form of the Boltzmann equation. Numerical results have demonstrated the effectiveness of the proposed method.

Tsallis statistics generalizes Boltzmann-Gibbs statistical mechanics through a single real parameter $q$ that controls the weight assigned to rare and frequent events. Originally proposed to describe physical systems with long-range correlations, multifractal geometry, and heavy-tailed fluctuations, the framework has become a recurring ingredient in modern artificial intelligence (AI): it underlies sparse attention mechanisms (\textsc{sparsemax} and $α$-\textsc{entmax}), maximum-entropy reinforcement learning with controllable exploration, robust and heavy-tailed probabilistic models, and a family of generalized loss functions and regularizers. This paper offers a structured perspective on where Tsallis statistics meets AI. We first review the mathematical core: $q$-entropy and its variational (maximum-entropy) foundation, the $q$-exponential and $q$-logarithm, the $q$-central limit theorem, $q$-Gaussian distributions, and their dynamical origin in superstatistics, emphasizing the properties that matter for machine learning. We then survey applications across softmax generalization, reinforcement learning, sequential and graph neural models, generative and probabilistic modeling, loss design, and optimization, extracting the recurring design pattern in each case: a tunable interpolation between dense/uniform and sparse/peaked behavior governed by $q$. We further argue that the heavy-tailed weight spectra and gradient-noise statistics empirically observed in deep networks are themselves nonextensive signatures, placing modern learning dynamics within the scope of $q$-statistics. Finally, we discuss methodological pitfalls, the relationship to information geometry and $q$-exponential families, and open directions, arguing that $q$ should be treated as a learnable inductive bias rather than a fixed hyperparameter.

We study the generative capabilities of Boltzmann machines to recover systems governed by the majority rule under critical conditions. To this end, we train deep belief networks (DBNs) with different configurations, where the first layer can use Gaussian visible units with more than two states (i.e., non-binary units). We then allow the DBN to "dream" samples conditioned on visible units that we keep fixed, and we measure the deviation of this dreamed system from the real one. We also corroborate, using a discrete thermometer based on a convolutional network, that the reconstructions remain in a critical state. Across several training sessions with different architectures, we show that, despite the complexity of the problem, the DBN can recover samples that remain critical even under input noise, with a gradual degradation of physical observables relative to the original sample.

Nuclear quantum effects are rigorously captured by imaginary-time path integrals, which map the quantum Boltzmann distribution onto a ring polymer of classical replicas. Yet the nuclear masses, the coupling to the environment, and the boundary conditions of the path remain hard-wired in the simulation or the trained model, even though this quantum context enters the path measure only through a quadratic action known in closed form. Here we show that a denoiser trained on classical Boltzmann statistics alone, composed at sampling time with an analytic Gaussian component carrying the entire quantum context, yields the quantum Boltzmann distribution of the nuclei. Such a composition exists and is exact whenever the training noise does not exceed the intrinsic quantum uncertainty of the target ensemble, and it is invariant across all quantum contexts admitted by this bound. We show exact transfer across temperature, isotopic mass, dissipation strength, and the boundary conditions of the path in theory and in numerical experiments, without retraining. The last yields the end-to-end displacement and momentum distributions of a tagged nucleus from open imaginary-time paths. The same invariance extends in principle to the permuted boundary conditions of bosonic exchange, with the identical denoiser. In this view, the noise of generative modeling and the quantum fluctuations of the nuclei are two faces of the same quadratic structure.

Most 3D properties relevant to molecular design, including free energies and shape descriptors, are $\textit{expectations}$ over the Boltzmann distribution over 3D configurations of a molecular graph. However, existing property-guided generative models tie each property to a single structure, ignoring the underlying ensemble. We recast 3D molecular design as $\textbf{Boltzmann-expected design}$ and realise it with $\textbf{DECAF}$ (Decoupled Annealing Flows), which factorise the joint distribution over graphs and coordinates into two conditional flow models: a graph-conditioned flow $p(x\mid\mathcal{G})$, acting as a $\textit{Boltzmann emulator}$, and a coordinate-conditioned flow $p(\mathcal{G}\mid x)$, proposing new graphs from 3D information. By alternating the two flows, DECAF optimises molecular graphs with a simulated-annealing acceptance rule whose scoring function is evaluated on ensembles drawn from $p(x\mid\mathcal{G})$, making ensemble statistics, not single-conformer properties, the design target. The resulting loop requires no retraining to change objectives. On GEOM-Drugs, we show that ensemble-aware optimisation produces graphs whose mean radius of gyration and solvent-accessible surface area consistently shift toward targets, while single-conformer optimisation degrades on larger drug-like molecules where Boltzmann distributions are broadest. DECAF extends to multi-objective trade-offs and, uniquely among 3D generative models, to $\textbf{higher-moment design}$: jointly optimising an ensemble property's variance and skewness to produce flexible molecules biased to a prescribed conformational regime: we verify the conformational distributions of these higher-moment designs with all-atom MD simulations.

Sampling from an unnormalized Boltzmann density requires proposals that move probability mass globally while retaining enough path-probability information for statistical correction. We introduce Neural Non-Equilibrium Hamiltonian Monte Carlo (NHMC), a train-then-correct learned Hamiltonian sampler. Starting from a tractable base distribution, NHMC learns stochastic Hamiltonian-style paths toward the target. Once training is complete, the learned proposal parameters are fixed; the proposal then generates complete paths and endpoint configurations, which are statistically corrected using the recorded non-equilibrium work. This dimensionless generalized work is determined by the probability ratio between the forward proposal path and a reverse reference path. During training, minimizing its mean reduces a path-space KL divergence and controls an upper bound on endpoint mismatch. During evaluation, the same quantity defines weights for self-normalized importance sampling on paths (path-SNIS), estimates normalizing constants or free-energy differences, and gives the acceptance ratio for path-space independent Metropolis-Hastings (path-IMH). The same forward-reverse laws also define a shared-bridge round-trip Metropolis kernel that acts directly on configurations and preserves the Boltzmann target. On double-well and finite-volume lattice $φ^4$ targets, the NHMC construction gives corrected estimates when path overlap is sufficient; when overlap is poor, weight degeneracy, low acceptance, and long autocorrelation expose proposal failure. We additionally report a molecular internal-coordinate feasibility study using an MD prior and learned-force path proposal.

Lattice field theory is the workhorse of non-perturbative physics, used to simulate phenomena from the strong nuclear force to critical phenomena in materials. Its Boltzmann distributions are parametrized analytically by coupling constants, but these bare parameters are weak predictors of observables -- extracting physics typically requires extensive simulation. While normalizing flows have emerged as effective samplers at fixed couplings, it remains difficult to interpret what these networks have learned. This raises a natural question: can the physics be read off directly from the flow network parameters themselves, and can those parameters be generated for unseen theories? We propose lattice field theory as a testbed for neural network interpretability: because the target physics is qualitatively well-understood and smoothly varying, it provides ideal synthetic data with known ground truth. To this end, we introduce JEPAWG, a Joint-Embedding Predictive Architecture-based Weight Generator that maps couplings directly to flow weights via a learned latent space. On a scalar theory at lattices of size $6^2$ to $11^2$, the JEPAWG latent space recovers the correct intrinsic dimension of the underlying manifold, locates the phase transition, and encodes a finite-size shift aligned with the 2D Ising exponent $ν\approx 1$, allowing us to uncover physical structure by studying the network weights alone. This suggests the fascinating idea of treating the network weights as a new type of physical observable. As a generator, JEPAWG also interpolates and extrapolates to unseen couplings effectively and remains robust to weight-space discontinuities introduced by multi-seed training data, outperforming PCA, AE, and VAE baselines.

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.

We design an algorithm for learning the coefficients of an $n$-qubit constant-local Lindbladian to $\varepsilon$ error with $O(g d^2 \log(n) / \varepsilon^2)$ total evolution time, where $g$ is the single-site energy and $d$ is the (approximate) degree of the interaction graph. Though Lindbladians present new challenges not present in the special case of Hamiltonians, our algorithm achieves the suite of desiderata attained by state-of-the-art Hamiltonian learning algorithms: (1) it uses non-adaptive, ancilla-free randomized Pauli measurement circuits with a time resolution of only $Θ(1/g)$; (2) it works without knowledge of the structure of the unknown Lindbladian; (3) it depends on a smooth form of degree, thereby supporting the learning of quasi-local and power-law Lindbladians. Our algorithm is a simple iterative method, where the objective function consists of Fourier coefficients of the Lindbladian restricted to few-site regions. Its analysis identifies the difficulty unique to open systems, which we call "confusing" terms. For settings where the "confusion" is limited, the performance of the algorithm improves. We demonstrate this for the case of structure learning of Hamiltonians from access to real-time evolution, where we obtain a new algorithm that is significantly simpler than previous work. In addition, using the same iterative method, we design the first efficient algorithm for structure learning Hamiltonians from high-temperature Gibbs states.

Recent progress in flow-based generative modeling has led to models that output high-quality samples while using only a small number of function evaluations. However, at present, there is a lack of similar advances in estimating the model likelihood. In particular, most existing methods either rely on restrictive architectures that enable exact calculations, or use stochastic approximations such as Hutchinson's trace estimator that introduce substantial variance. In this work, we introduce SCAlable LikeLihood distillation of flOw maPs (SCALLOP). SCALLOP builds on the recently proposed F2D2, a likelihood flow map model that can generate samples and their densities in a small number of function evaluations. While F2D2 uses Hutchinson's estimator during training, we introduce an alternative and more scalable likelihood distillation objective that is Hutchinson-free and admits a vectorized formulation. Empirically, we demonstrate the effectiveness of SCALLOP as a Boltzmann generator in molecular science, and further validate its benefit on image datasets. SCALLOP significantly reduces both training variance and training time while consistently improving performance compared to F2D2, and is competitive with the state-of-the-art while achieving up to 10x inference speedup over the fastest baseline.

Efficient sampling of molecular systems at thermodynamic equilibrium is a hallmark challenge in statistical physics. This challenge has driven the development of Boltzmann Generators (BGs), which allow rapid generation of uncorrelated equilibrium samples by combining a generative model with exact likelihoods and an importance sampling correction. However, modern BGs predominantly rely on normalizing flows (NFs), which either suffer from limited expressivity due to strict invertibility constraints (discrete time) or computationally expensive likelihoods (continuous time). In this paper, we propose Autoregressive Boltzmann Generators (ArBG) -- a novel autoregressive modelling framework -- that overcomes these limitations by departing from the flow-based BG paradigm. ArBG circumvents the topological constraints of flows and enables sequential inference-time interventions, while offering enhanced scalability by leveraging architectures effective in Large Language Models. We empirically demonstrate that ArBG leads to significant improvements over flow-based models across all benchmarks, but particularly in larger peptide systems such as the 10-residue Chignolin. Furthermore, we introduce Robin, a 132 million parameter transferable model trained with the ArBG framework which improves over the previous state-of-the-art, reducing the zero-shot energy error, E-W$_2$, on 8-residue systems by over 60$\%$. The code can be found at the following link: https://github.com/danyalrehman/autobg.

Particle-based variational inference (ParVI) methods approximate an intractable target distribution by evolving an ensemble of interacting samples. Existing approaches rely predominantly on kernel-based repulsion (e.g., SVGD), which suffers from variance collapse in high dimensions and mode collapse on multimodal targets -- pathologies caused by the absence of global transport structure. We introduce entropic transport descent (ETD), a ParVI family that frames each particle update as an entropy-regularized optimal transport problem. Derived from the JKO proximal scheme by lifting to the space of couplings and relaxing via the KL chain rule, each ETD iteration reduces to a Sinkhorn computation. The resulting transport plan provides global coordination, guiding each particle to nearby high-density proposals and naturally preserving multimodal structure. ETD can operate entirely score-free, requiring only pointwise evaluations of the unnormalized target density. Experiments on variance-collapse diagnostics, Bayesian logistic regression, neural networks, and molecular Boltzmann distributions show that ETD matches or outperforms SVGD, AGF-SVGD, and SGLD, with the largest gains in high-dimensional and multimodal settings.

Efficient sampling of the Boltzmann distribution in frustrated spin glasses is central to statistical mechanics and combinatorial optimization. Despite advances in machine-learning-based approaches, two issues persist: limited understanding of why variational models fail to benefit from increased scale, unlike the monotonic scaling law of large language models; and high computational cost on large systems that negates advantages over classical sampling methods. Here, we develop a physics-inspired transformer with interpretable sparse attention and spin-tailored positional embeddings to address these challenges. By further leveraging FlashAttention for parallel ancestral sampling, it achieves up to two orders of magnitude speedup over vanilla variational autoregressive networks, enabling neural-network simulations of spin-glass systems to unprecedented sizes on a single GPU. It can resolve full probability distributions, free energies, and overlap statistics across temperatures, for Sherrington-Kirkpatrick and 2D or 3D Edwards-Anderson models, where existing machine-learning methods encounter limitations at certain temperatures. This framework thus establishes a scalable paradigm for frustrated spin-glass systems.

To leading order under local asymptotic normality (LAN), the confidence density a worker emits over a chunk of size $n$ is a Gibbs--Boltzmann measure $\exp\{-βE(θ)\}$ whose inverse temperature is the sample size, $β=n$. Three consequences are exact in the Gaussian/linear case and first-order otherwise: disjoint chunks carry independent Boltzmann factors, so the MapReduce \emph{reduce}, read literally, is a partition function $Z=\int\prod_k h_k\,dθ$ whose mode is precision-weighted (inverse-variance) pooling; frequentist consistency is the zero-temperature limit $T=1/n\to0$

Convergence-rate analysis for classifiers is often conducted under either Tsybakov margin or Massart margin. The former is a relatively weak condition that typically yields polynomial rates, while the latter is substantially stronger but can guarantee exponential rates. In this paper, we introduce a new condition, called Boltzmann margin, that bridges the gap between these two regimes. It is weaker than Massart margin, generally stronger than Tsybakov margin, and can imply many of their properties under suitable conditions. We apply Boltzmann margin to the analysis of kNN classifiers and establish the first near-exponential convergence rates for kNN classification. We also present extensions of the main results and provide numerical evidence supporting the main theoretical implications.

A long standing challenge in computational chemistry and biophysics is efficiently sampling the Boltzmann distribution of molecules. Advances in generative modeling have been proposed to address the limitations of conventional sampling techniques by eliminating the computational cost of simulation. A promising direction is iteratively finetuning diffusion models along a temperature ladder whereby training data is generated via importance sampling during inference-time annealing. Unfortunately, these methods require computing a divergence over the score field to estimate importance weights, rendering them intractable for larger systems. Here we present scalable inference-time annealing (SITA), which retrains flow-based models to generate samples at progressively lower temperatures using an energy-based model to facilitate fast surrogate likelihoods. We demonstrate state-of-the-art performance on both Alanine Dipeptide and Alanine Tripeptide while avoiding costly divergence terms. Our code is available at https://github.com/countrsignal/sita.git

In this article, we present an improved version of the PULSE method (Partition function Unsupervised Learning Sampling and Evaluation) for estimating the thermodynamic properties of chemically disordered compounds. The aim is to reduce the computational cost of Monte Carlo approaches for this type of material and to demonstrate that this generative tool can estimate thermodynamic properties by sampling and estimating the partition function of the system. To validate this innovative approach, we use the 2D Ising model as a benchmark. We demonstrate that our method accurately reproduces average properties with high precision and efficiency compared to traditional Monte Carlo sampling methods. Our results highlight the efficiency and adaptability of the PULSE method, making it a valuable tool for studying materials for which conventional methods are too inefficient to compute properties affected by chemical disorder at low cost.

Discrete diffusion models have achieved strong empirical performance in text and other symbolic domains, but, especially for uniform-rate models, they often require many steps to generate a single sample. Existing acceleration methods either rely on training additional quantities or suffer from slow mixing. In this work, we propose a novel Gibbs-based corrector for discrete diffusion models, termed Gibbs-Accelerated Discrete Diffusion (GADD). GADD leverages the structure of the concrete score function to construct Gibbs posterior likelihoods directly, without requiring any additional training beyond standard score estimation. We show that GADD achieves an overall sampling complexity of $\mathcal{O}(\mathrm{polylog} (\varepsilon^{-1}))$, yielding the first such rate for diffusion-based samplers for uniform-rate discrete diffusion models. We also conduct numerical experiments demonstrating the practical advantages of GADD across synthetic data, zero-shot text sampling, and zero-shot conditional music generation. These results corroborate the theory and show that GADD consistently improves sample quality and wall-clock efficiency over standard baselines, including vanilla Euler methods and CTMC correctors. Beyond this, our theoretical analysis introduces a novel framework for analyzing predictor-corrector methods in discrete diffusion models, which may be of independent interest. Unlike existing approaches that rely on the Girsanov change-of-measure technique, our method is based on an induction argument that tracks error propagation across predictor iterations while accounting for inaccuracies in the corrector updates.

Molecules in equilibrium follow a Boltzmann distribution, making the underlying energy landscape a physically grounded modeling objective. However, such landscapes are difficult to learn from data and, once learned, hard to sample from. Diffusion and flow-matching models sidestep these difficulties by learning a time-conditional score or transport field between noise and data, losing the energy inductive bias in exchange for a more tractable training objective. We introduce EBMol, an energy-based model (EBM) that restores this inductive bias by learning an atom-additive scalar potential without explicit simulation during training. Our method employs a flow-inspired Restoring Field Matching objective to approximate the energy landscape. We adopt the Mirror-Langevin algorithm for sampling, enabling unified updates of atomic positions and types, and incorporate parallel tempering for inference-time compute scaling. EBMol is the first EBM for 3D molecular generation to achieve state-of-the-art performance on QM9 and GEOM-Drugs. Moreover, we show that the learned energy landscape serves as a principled quality metric for ranking and filtering configurations, and demonstrate controllable generation without retraining through shape-steered sampling via potential composition and zero-shot linker design.

We consider the active learning problem where the goal is to learn an unknown function with low prediction error under an unknown Boltzmann distribution induced by the function itself. This self-induced weighting arises naturally in problems such as potential energy surface (PES) modeling in computational chemistry, yet poses unique challenges as the target distribution is unknown and its partition function is intractable. We propose \texttt{AB-SID-iVAR}, a Gaussian Process-based acquisition function that approximates the intractable Bayesian target distribution in closed form while avoiding partition function estimation, and is applicable to both discrete and continuous input domains. We also analyze a Thompson sampling alternative (\texttt{TS-SID-iVAR}) as a higher variance Monte Carlo variant. Despite the unknown target, under mild conditions, we establish that the terminal prediction error vanishes with high probability, and provide a tighter average-case guarantee. We demonstrate consistent improvements over existing approaches in this setting on synthetic benchmarks and real-world PES modeling and drug discovery tasks.

Knowledge of a protein's atomic conformational ensemble is critical to determining its function, yet state-of-the-art ensemble prediction models are limited by lack of high-quality conformational data from simulation or experiment. Recent advances in heterogeneous reconstruction for cryo-electron microscopy (cryo-EM) have enabled scientists to visualize ensembles of density maps for larger proteins and complexes not typically accessible through simulation, but building atomic models into these maps remains a challenge. Traditionally, ensemble prediction models are trained via a two-stage process: experimental density maps are converted into atomic structural ensembles through model building, after which these structures are used to train sequence-to-atomic ensemble predictors. In this work, we propose a new principle for fine-tuning pre-trained static structure prediction models such as Boltz-2 directly on raw cryo-EM maps, bypassing the two-stage process. We apply this technique to the problem of atomic model building by fine-tuning Boltz-2 to generate atomic conformations from an input ensemble of cryo-EM maps, achieving superior model building accuracy compared to prior work. Beyond overfitting to individual map ensembles, our method, CryoSampler, also shows preliminary evidence of in-domain generalization after fine-tuning, sampling diverse atomic conformations for an unseen sequences within the same protein family without requiring cryo-EM data. These capabilities indicate that CryoSampler holds the potential to train next-generation atomic ensemble prediction models directly on raw cryo-EM measurements.

Energy-based models (EBMs) are flexible generative architectures inspired by statistical physics, but their learning and generative properties remain poorly understood. Here, we analyze a solvable EBM in the high-dimensional limit: the spherical Boltzmann machine (SBM). Combining tools from random matrix theory and dynamical mean-field theory, we: solve exact equations describing the training dynamics of the SBM; compute the Bayesian evidence, which acts as a partition function in parameter space and encodes global properties of the trained model; and uncover cascades of phase transitions that occur both during training and as a function of hyperparameters, related to successive alignment and condensation of the top modes of the coupling matrix to the data. We connect these transitions to sampling-time generative phenomena in a teacher-student scenario, including: sampling temperature tuning, double descent as a function of regularization strength, tempered posterior effects, and out-of-equilibrium effects during training that induce biases in the trained model. We provide numerical evidence demonstrating that all these phenomena appear in standard generative architectures, beyond the SBM.

Reinforcement learning (RL) has shown extraordinary potential in aligning diffusion models to downstream tasks, yet most of them still suffer from significant reward hacking, which degrades generative diversity and quality by inducing visual mode collapse and amplifying unreliable rewards. We identify the root cause as the mode-seeking nature of these methods, which maximize expected reward without effectively constraining probability distribution over acceptable trajectories, causing concentration on a few high-reward paths. In contrast, we propose Trajectory Matching Policy Optimization (TMPO), which replaces scalar reward maximization with trajectory-level reward distribution matching. Specifically, TMPO introduces a Softmax Trajectory Balance (Softmax-TB) objective to match the policy probabilities of K trajectories to a reward-induced Boltzmann distribution. We prove that this objective inherits the mode-covering property of forward KL divergence, preserving coverage over all acceptable trajectories while optimizing reward. To further reduce multi-trajectory training time on large-scale flow-matching models, TMPO incorporates Dynamic Stochastic Tree Sampling, where trajectories share denoising prefixes and branch at dynamically scheduled steps, reducing redundant computation while improving training effectiveness. Extensive results across diverse alignment tasks such as human preference, compositional generation and text rendering show that TMPO improves generative diversity over state-of-the-art methods by 9.1%, and achieves competitive performance in all downstream and efficiency metrics, attaining the optimal trade-off between reward and diversity.

Stochastic trajectory optimization methods like STOMP enable planning with non-differentiable costs, offering substantial flexibility over gradient-based approaches. We show that STOMP implicitly minimizes the KL divergence from a Boltzmann trajectory distribution, revealing an elegant Variational Inference (VI) structure underlying its updates. Building on this insight, we propose the \textit{Proximal Inference for Stochastic Trajectory Optimization} (PISTO) algorithm that stabilizes the updates by augmenting the objective with a KL regularization between successive Gaussian proposals. This proximal formulation admits a trust-region interpretation and yields closed-form mean updates computable as expectations under a surrogate distribution. We estimate these expectations via importance-weighted Monte Carlo sampling, producing a simple, derivative-free algorithm that inherits STOMP's ability to handle non-differentiable and discontinuous costs without modification. On robot arm motion planning benchmarks, PISTO achieves an 89% success rate -- outperforming CHOMP (63%) and STOMP (68%) -- while producing shorter, smoother paths at twice the speed of competing stochastic methods. We further validate PISTO on contact-rich MuJoCo locomotion and manipulation tasks, where it consistently outperforms both CEM and MPPI baselines in reward.

These lecture notes introduce some topics of classical statistical physics, particularly those that are relevant for neural networks and deep learning. Statistical physics is treated as a branch of probability theory or statistics, with the goal of making concepts such as phase transitions and the renormalization group accessible to readers without prior knowledge of physics. We introduce the Boltzmann-Gibbs distribution and the thermodynamic potentials on a finite configuration space, notably for Ising spins and spin-glass models on a lattice, and then define phase transitions as discontinuities that arise in the limit that the number of lattice points goes to infinity. We further introduce Hopfield networks and Boltzmann machines, which are governed by the same energy function as spin-glass models, and discuss the learning algorithm for restricted Boltzmann machines. In this algorithm hidden neurons are integrated out as in the renormalization group. Finally, modern deep learning is introduced, whose early developments were in part motivated by restricted Boltzmann machines in that they carry many layers of hidden neurons. A description of large language models is given.

Online reinforcement learning with verifiable rewards (RLVR) turns checkable outcomes into a scalable training signal, but it keeps rollout generation, verifier scoring, and reference-policy evaluations on the optimization path. Static weighted supervised fine-tuning (SFT) on precomputed rollouts seems to remove this bottleneck, yet a weighted likelihood is not specified by rewards alone: its sampler and weights induce the policy being fit. This paper identifies the reference-sampled weighted-SFT objective whose induced policy equals the fixed-reference KL-regularized RLVR optimizer. The optimizer is the standard Boltzmann target policy, obtained by exponentially tilting the reference policy by verifier reward. Matching a weighted-SFT induced policy to this target forces density-ratio weights; in the reference-sampled subclass, this reduces uniquely, up to prompt scaling, to the prompt-normalized Boltzmann weight $\exp(r(x,y)/β)/Z(x)$. BOLT, a Boltzmann-Targeted SFT procedure, is the empirical estimator of this projection. The finite one-shot analysis separates the exact stored-support price $β\log(1/π^*(S_N\mid x))$ from partition estimation, effective-sample-size variance, generalization, optimization, and approximation errors. This decomposition explains why extra SFT epochs cannot repair missing reference-policy coverage and exposes the temperature--coverage--variance frontier. When coverage needs adaptive sampling, refreshed Boltzmann projections become KL policy mirror descent; finite inner solves enter as additive drift from the exact mirror step. Single-run Qwen experiments provide projection evidence for the target-matched weight, one-shot saturation, refreshed-sampler gains, and optimization-time savings, within the stated single-run scope.

Exponential families encompass the distributions central to modern machine learning -- softmax, Gaussians, and Boltzmann distributions -- and underlie the theory of variational inference, entropy-regularized reinforcement learning, and RLHF. We isolate a simple identity for exponential families that expresses the KL difference $\mathrm{KL}(q \| p_{λ_2}) - \mathrm{KL}(q \| p_{λ_1})$ in terms of the log-partition function $A(λ)$ and the moment $μ_q$. Remarkably, this identity together with the single fact that $\mathrm{KL} \geq 0$ (with equality iff $p = q$) suffices, by direct substitution and rearrangement, to derive a cluster of results that are classically obtained by separate, heavier arguments: a generalized three-point identity for arbitrary reference distributions, Pythagorean theorems for I-projections and reverse I-projections, convexity of the log-partition function, identification of its Legendre dual in KL terms, the Gibbs variational principle, and the explicit optimizer in KL-regularized reward maximization, including the exponential tilting formula underlying entropy-regularized control and RLHF. Beyond these purely algebraic consequences, standard analytic arguments recover the gradient formula for the log-partition function, the Bregman representation of within-family KL divergence, and the surjectivity of the moment map. The note is self-contained.

Sampling from unnormalized probability densities is a central challenge in computational science. Boltzmann generators are generative models that enable independent sampling from the Boltzmann distribution of physical systems at a given temperature. However, their practical success depends on data-efficient training, as both simulation data and target energy evaluations are costly. To this end, we propose off-policy log-dispersion regularization (LDR), a novel regularization framework that builds on a generalization of the log-variance objective. We apply LDR in the off-policy setting in combination with standard data-based training objectives, without requiring additional on-policy samples. LDR acts as a shape regularizer of the energy landscape by leveraging additional information in the form of target energy labels. The proposed regularization framework is broadly applicable, supporting unbiased or biased simulation datasets as well as purely variational training without access to target samples. Across all benchmarks, LDR improves both final performance and data efficiency, with sample efficiency gains of up to one order of magnitude.

Fixed points of recurrent neural networks can be leveraged to store and generate information. These fixed points are captured by the Boltzmann-Gibbs measure, which leads to neural Langevin dynamics that relax to those fixed points for generative learning of a real dataset. We call this type of generative model a neural Langevin machine, which derives an asymmetric and firing-rate-speed-adjusted learning rule requiring only local neural signals, thereby bearing biological relevance in terms of local predictive learning. An out-of-equilibrium regime of the generative process is revealed, together with a memorization-to-generalization transition with increasing training data size. The neuro-inspired machine can also realize a continuous exploration of the phase space for different kinds of generative images and can denoise a corrupted image as well.