Proteins mediate their functions through chemical interactions; modeling these interactions, which are typically through sidechains, is an important need in protein design. However, constructing an all-atom generative model requires an appropriate scheme for managing the jointly continuous and discrete nature of proteins encoded in the structure and sequence. We describe an all-atom diffusion model of protein structure, Protpardelle, which represents all sidechain states at once as a “superposition” state; superpositions defining a protein are collapsed into individual residue types and conformations during sample generation. When combined with sequence design methods, our model is able to codesign all-atom protein structure and sequence. Generated proteins are of good quality under the typical quality, diversity, and novelty metrics, and sidechains reproduce the chemical features and behavior of natural proteins. Finally, we explore the potential of our model to conduct all-atom protein design and scaffold functional motifs in a backbone- and rotamer-free way.

中文翻译：

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全原子蛋白质生成模型


蛋白质通过化学相互作用介导其功能；对这些通常通过侧链进行的相互作用进行建模是蛋白质设计中的一个重要需求。然而，构建全原子生成模型需要适当的方案来管理结构和序列中编码的蛋白质的联合连续和离散性质。我们描述了蛋白质结构的全原子扩散模型 Protpardelle，它同时将所有侧链状态表示为“叠加”状态；定义蛋白质的叠加在样品生成过程中被分解为单独的残基类型和构象。当与序列设计方法相结合时，我们的模型能够共同设计全原子蛋白质结构和序列。生成的蛋白质在典型的质量、多样性和新颖性指标下具有良好的质量，并且侧链再现了天然蛋白质的化学特征和行为。最后，我们探索了我们的模型以无主链和旋转异构体的方式进行全原子蛋白质设计和支架功能基序的潜力。