BMAIApr 23, 2025

The Dance of Atoms-De Novo Protein Design with Diffusion Model

arXiv:2504.16479v1h-index: 2
Originality Synthesis-oriented
AI Analysis

This work addresses the problem of designing novel proteins with specific structures and functions for researchers in biotechnology and medicine, but it is incremental as it reviews existing advancements rather than introducing new methods.

The paper reviews the application of diffusion models in de novo protein design, highlighting that these models, such as RFDiffusion, have significantly improved success rates over traditional methods, with RFDiffusion achieving high success in 25 design tasks.

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological advancements have paved the way for the successful application of generative artificial intelligence (AI) models in protein design. These models have surpassed traditional approaches that rely on fragments and bioinformatics. They have significantly enhanced the success rate of de novo protein design, and reduced experimental costs, leading to breakthroughs in the field. Among various generative AI models, diffusion models have yielded the most promising results in protein design. In the past two to three years, more than ten protein design models based on diffusion models have emerged. Among them, the representative model, RFDiffusion, has demonstrated success rates in 25 protein design tasks that far exceed those of traditional methods, and other AI-based approaches like RFjoint and hallucination. This review will systematically examine the application of diffusion models in generating protein backbones and sequences. We will explore the strengths and limitations of different models, summarize successful cases of protein design using diffusion models, and discuss future development directions.

Foundations

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