Breaking the Bottlenecks: Scalable Diffusion Models for 3D Molecular Generation

TL;DR

This paper introduces a deterministic diffusion model for 3D molecular generation that improves efficiency, stability, and structural fidelity by leveraging a new theoretical framework called RTK, addressing key bottlenecks in existing stochastic models.

Contribution

The work provides a theoretical reinterpretation of deterministic denoising in diffusion models using the RTK framework, enhancing understanding and addressing limitations in molecular generation.

Findings

Faster convergence compared to stochastic models

Higher structural fidelity in generated molecules

Maintains chemical validity across datasets

Abstract

Diffusion models have emerged as a powerful class of generative models for molecular design, capable of capturing complex structural distributions and achieving high fidelity in 3D molecule generation. However, their widespread use remains constrained by long sampling trajectories, stochastic variance in the reverse process, and limited structural awareness in denoising dynamics. The Directly Denoising Diffusion Model (DDDM) mitigates these inefficiencies by replacing stochastic reverse MCMC updates with deterministic denoising step, substantially reducing inference time. Yet, the theoretical underpinnings of such deterministic updates have remained opaque. In this work, we provide a principled reinterpretation of DDDM through the lens of the Reverse Transition Kernel (RTK) framework by Huang et al. 2024, unifying deterministic and stochastic diffusion under a shared probabilistic formalism. By expressing the DDDM reverse process as an approximate kernel operator, we show that the direct denoising process implicitly optimizes a structured transport map between noisy and clean samples. This perspective elucidates why deterministic denoising achieves efficient inference. Beyond theoretical clarity, this reframing resolves several long-standing bottlenecks in molecular diffusion. The RTK view ensures numerical stability by enforcing well-conditioned reverse kernels, improves sample consistency by eliminating stochastic variance, and enables scalable and symmetry-preserving denoisers that respect SE(3) equivariance. Empirically, we demonstrate that RTK-guided deterministic denoising achieves faster convergence and higher structural fidelity than stochastic diffusion models, while preserving chemical validity across GEOM-DRUGS dataset. Code, models, and datasets are publicly available in our project repository.