Drifting to Boltzmann: Million-Fold Acceleration in Boltzmann Sampling with Force-Guided Drifting

TL;DR

This paper introduces force-guided drifting models for molecular conformation sampling, achieving over a million-fold acceleration over traditional methods while maintaining accuracy and structural validity.

Contribution

It establishes a theoretical framework linking drifting models to Boltzmann sampling and introduces novel force incorporation techniques for efficient one-step molecular conformation generation.

Findings

Over 1000x speedup on MD17 Ethanol dataset

Achieves million-fold acceleration over traditional molecular dynamics

Maintains structural validity and distributional accuracy

Abstract

Sampling molecular conformations from the Boltzmann distribution is essential for computational chemistry, but iterative diffusion methods are prohibitively slow. Drifting Models offer one-step generation, yet their equilibrium matches the \emph{training} distribution, which may deviate from the true Boltzmann distribution due to sampling bias. We introduce Drifting Models to molecular conformation generation for the first time, establishing a theoretical bridge via the \emph{Drifting Score Identity}: for Gaussian kernels, the drifting field's attraction equals a kernel-weighted average of \emph{any} distribution's score function. Substituting molecular force labels -- which directly encode the Boltzmann score -- yields the \emph{Drifting Force Identity} and decomposes the field into standard drift plus a Boltzmann correction. We further discover a striking phenomenon unique to molecular systems: force incorporation's effectiveness \emph{reverses across representations}. In coordinate space, Force-Interpolated Drifting (FI) dominates by blending physical force directions with data displacements. In distance feature space, Force-Aligned Kernel (FK) achieves superior accuracy by modifying only kernel weights, thereby preserving the manifold of geometrically valid molecules. On MD17 Ethanol, both approaches achieve one-step generation with over 1000x speedup relative to recent score-matching methods with Boltzmann guiding, providing more than million-fold acceleration over traditional molecular dynamics, while ensuring perfect structural validity and distributional accuracy rivaling multi-step methods.