结论表明:通过pAE过滤的序列库在IL2RA和LTK靶点上对比Rosetta-based的过滤方法,得到binder的数量分别有8,30倍的差异,更重要的是,在具有挑战性的靶点IL-10Rɑ和ALK靶点也成功设计出来了binder! 3.2 引入MPNN替代FastDesign 众所周知,近期发布的ProteinMPNN在CPU上的设计效率已证实远超Rosetta FastDesign(2s vs 350s ...
Hallucination中看似简单的改动,就完成了自洽地生成蛋白结构和对应的序列,达到无中生有的境界,最后作者也提出了鲜明的观点,Hallucination+trDesign的设计方式完全可以来解决功能片段的融合设计问题,潜在的应用场景是酶设计、金属结合蛋白,以及蛋白binder设计,也是下一章节的主要内容。 3trDesign-Motif 文献参考:Tischer D, ...
Designing peptides that bind to specific protein targets is crucial for peptidic drug development, however, traditional computer-aided binder design is outperformed by AlphaFold2. Here, the authors develop a peptide binder designing tool by combining Foldseek, ESM-IF1 and AlphaFold2 to increase the...
et al. Improving de novo protein binder design with deep learning. Nat. Commun. 14, 2625 (2023). CAS PubMed PubMed Central ADS Google Scholar Glasscock, C. J. et al. Computational design of sequence-specific DNA-binding proteins. Preprint at bioRxiv https://doi.org/10.1101/2023.09....
et al. Robust deep learning-based protein sequence design using ProteinMPNN. Science 378, 49–56 (2022). Article Google Scholar Bennett, N. R. et al. Improving de novo protein binder design with deep learning. Nat. Commun. 14, 2625–2633 (2023). Article Google Scholar Bryant, P. &...
The cryo-electron microscopy (cryo-EM) structures of the mini protein binder in complex with TcdB1 and TcdB4 are consistent with the computational design models. The engineered and evolved variants of the mini-protein binder and chondroitin sulfate proteoglycan 4 (CSPG4), another natural receptor...
Why risk matters for protein binder design [arXiv:2504.00146] Systematic comparison of Generative AI-Protein Models reveals fundamental differences between structural and sequence-based approaches [bioRxiv 2025.03.23.644844] • [code] • [Supplementary] Deep Learning-Driven Protein Structure Predicti...
denoising tasks, we obtain a generative model of protein backbones that achieves outstanding performance on unconditional and topology-constrained protein monomer design, protein binder design, symmetric oligomer design, enzyme active site scaffolding and symmetric motif scaffolding for therapeutic and metal-...
Ligand GA is introduced in this work and approaches the problem of finding small molecules inhibiting protein functions by using the protein site to find close to optimal or optimal small molecule binders. Genetic algorithms (GA) are an effective means f
converting a generic protein into a specific binder). We also note that taking advantage of this strategy for guiding evolution may be more difficult when the selection pressure is unnatural or if the wild-type sequence is already at a fitness peak. However, in many practical design tasks, nat...