在第二个靶点上,同样的思路进行复制:MaSIF-seed找到了高度收敛的12个residue长度的螺旋片段,并使用Rosetta motif-graft将螺旋移植到了5个不同的scaffold上和进化筛选,同样得到了针对PD-1的binder。 2.3 改进的binder设计流程 上述的实验虽然是成功的,但设计流程都需要通过酵母展示来进化和筛选,以获得可检测的亲和力bin...
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 ...
In this work, we develop a deep learning-augmented de novo protein binder design protocol. We show retrospectively and prospectively that this improved protocol has nearly 10-fold higher success rate than the original energy-based method. Results Retrospective analysis of type I failures We began by...
There has been considerable recent progress in designing new proteins using deep-learning methods1,2,3,4,5,6,7,8,9. Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de novo binder design and desig...
De novo protein design can now generate binders with high affinity and specificity to structured proteins. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for ...
这次的进步主要是颠覆了以往严重依赖于预先生成的scaffold数据库的问题,让基于motif设计de novo蛋白有了更具广阔的结构模板空间。虽然没有解决之前遗留的trRosetta模型精度有限的问题,依然需要配合Rosetta FastDesign来输出最后的序列,但我们离真正地实现”一键蛋白质设计“更近了一步。另外本文方法的另外一个严重缺陷的问题...
Fig. 1: Surface-centric design of de novo site-specific protein binders. a, Schematic of fingerprint generation. Protein binding sites are spatially embedded as vector fingerprints. Protein surfaces are decomposed into overlapping radial patches, and a neural network trained on native interacting prote...
including de novo binder design and design of higher-order symmetric architectures, has yet to be described. Diffusion models10,11have had considerable success in image and language generative modelling but limited success when applied to protein modelling, probably due to the complexity of protein ba...
we chose to de novo design mini-protein binders as the starting point. These mini-protein binders were later developed into a broad neutralizing binder H3, which binds to major clinical TcdB variants (TcdB1-4) with sub-nanomolar affinities. Cryo-EM structures of mini-protein binder 43829 bound...
De novo 3FTx binder design using RFdiffusion The crystal structures of ScNtx (PDB7Z14) and α-cobratoxin (PDB1YI5) served as the inputs for RFdiffusion. In the case of the consensus cytotoxin, the AF2 model was used. Approximately 2,000 diffused designs were generated for each target, ...