EC-Conf: A ultra-fast diffusion model for molecular conformation generation with equivariant consistency

• Published in: Journal of cheminformatics Vol. 16; no. 1; pp. 107 - 15
• Main Authors: Fan, Zhiguang, Yang, Yuedong, Xu, Mingyuan, Chen, Hongming
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 03.09.2024; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Chemistry; Chemistry and Materials Science; Computational Biology/Bioinformatics; Computer Applications in Chemistry; Conformation generation; Diffusion; Diffusion rate; Documentation and Information in Chemistry; Drug development; Efficiency; Energy distribution; Iterative methods; Molecular conformation; Molecular modelling; Molecular structure; Noise reduction; Performance evaluation; Protein structure; Proteins; Sampling; Task complexity; Theoretical and Computational Chemistry; Ultra-fast diffusion models; Conformation generation; Ultra-fast diffusion models
• ISSN: 1758-2946; 1758-2946
• DOI: 10.1186/s13321-024-00893-2

Despite recent advancement in 3D molecule conformation generation driven by diffusion models, its high computational cost in iterative diffusion/denoising process limits its application. Here, an equivariant consistency model (EC-Conf) was proposed as a fast diffusion method for low-energy conformation generation. In EC-Conf, a modified SE (3)-equivariant transformer model was directly used to encode the Cartesian molecular conformations and a highly efficient consistency diffusion process was carried out to generate molecular conformations. It was demonstrated that, with only one sampling step, it can already achieve comparable quality to other diffusion-based models running with thousands denoising steps. Its performance can be further improved with a few more sampling iterations. The performance of EC-Conf is evaluated on both GEOM-QM9 and GEOM-Drugs sets. Our results demonstrate that the efficiency of EC-Conf for learning the distribution of low energy molecular conformation is at least two magnitudes higher than current SOTA diffusion models and could potentially become a useful tool for conformation generation and sampling. Scientific Contributions In this work, we proposed an equivariant consistency model that significantly improves the efficiency of conformation generation in diffusion-based models while maintaining high structural quality. This method serves as a general framework and can be further extended to more complex structure generation and prediction tasks, including those involving proteins, in future steps. Key points A novel ultra-fast equivariant diffusion model, EC-Conf, was proposed for low-energy conformation generation by construction of a consistency process. Compared with other SOTA diffusion models running with thousands denoising steps, EC-Conf can achieve comparable quality with only one sampling step and keep improving with a few more sampling iterations. The efficiency of EC-Conf is at least two magnitudes higher than current SOTA diffusion models. The EC-Conf is universal and can be easily extended to various conformation generation tasks such as protein–ligand docking pose.