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 free energy


Phase transitions in Doi-Onsager, Noisy Transformer, and other multimodal models

Mun, Kyunghoo, Rosenzweig, Matthew

arXiv.org Machine Learning

We study phase transitions for repulsive-attractive mean-field free energies on the circle. For a $\frac{1}{n+1}$-periodic interaction whose Fourier coefficients satisfy a certain decay condition, we prove that the critical coupling strength $K_c$ coincides with the linear stability threshold $K_\#$ of the uniform distribution and that the phase transition is continuous, in the sense that the uniform distribution is the unique global minimizer at criticality. The proof is based on a sharp coercivity estimate for the free energy obtained from the constrained Lebedev--Milin inequality. We apply this result to three motivating models for which the exact value of the phase transition and its (dis)continuity in terms of the model parameters was not fully known. For the two-dimensional Doi--Onsager model $W(θ)=-|\sin(2πθ)|$, we prove that the phase transition is continuous at $K_c=K_\#=3π/4$. For the noisy transformer model $W_β(θ)=(e^{β\cos(2πθ)}-1)/β$, we identify the sharp threshold $β_*$ such that $K_c(β) = K_\#(β)$ and the phase transition is continuous for $β\leq β_*$, while $K_c(β) β_*$. We also obtain the corresponding sharp dichotomy for the noisy Hegselmann--Krause model $W_{R}(θ) = (R-2π|θ|)_{+}^2$ .


Enhanced Diffusion Sampling: Efficient Rare Event Sampling and Free Energy Calculation with Diffusion Models

Xie, Yu, Winkler, Ludwig, Sun, Lixin, Lewis, Sarah, Foster, Adam E., Luna, José Jiménez, Hempel, Tim, Gastegger, Michael, Chen, Yaoyi, Zaporozhets, Iryna, Clementi, Cecilia, Bishop, Christopher M., Noé, Frank

arXiv.org Machine Learning

The rare-event sampling problem has long been the central limiting factor in molecular dynamics (MD), especially in biomolecular simulation. Recently, diffusion models such as BioEmu have emerged as powerful equilibrium samplers that generate independent samples from complex molecular distributions, eliminating the cost of sampling rare transition events. However, a sampling problem remains when computing observables that rely on states which are rare in equilibrium, for example folding free energies. Here, we introduce enhanced diffusion sampling, enabling efficient exploration of rare-event regions while preserving unbiased thermodynamic estimators. The key idea is to perform quantitatively accurate steering protocols to generate biased ensembles and subsequently recover equilibrium statistics via exact reweighting. We instantiate our framework in three algorithms: UmbrellaDiff (umbrella sampling with diffusion models), $Δ$G-Diff (free-energy differences via tilted ensembles), and MetaDiff (a batchwise analogue for metadynamics). Across toy systems, protein folding landscapes and folding free energies, our methods achieve fast, accurate, and scalable estimation of equilibrium properties within GPU-minutes to hours per system -- closing the rare-event sampling gap that remained after the advent of diffusion-model equilibrium samplers.