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Anthropic 使用 Claude 显示细菌和 Phage 蛋白质形态
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Anthropic于2026年11月4日报告了结果，显示主要金库蛋白的亲缘亲缘关系在E.coli生产时可以组装成金库颗粒。 Claude帮助团队以3.2 angstroms的名义分辨率绘制出一枚细菌衍生壳。
假体是大型空心蛋白壳，其生物功能仍不明。 在细菌中产生相关的颗粒，使研究人员有一个更快的生长系统来调查它们的组装、内装和起源。 Anthropic将L05结果描述为在prokaryotic细胞中发现的金库粒子的第一个3D结构。 这项工作建立了组装和建筑，同时使生物功能得不到解决。
从蛋白质搜索到确认的断层
使用 Claude 科学，研究者们搜索了大约150亿预测蛋白质的数据库。 他们在29个细菌phyla和4个考古phyla中发现了主要的金库蛋白同位素，尽管这些蛋白质出现在只有序列基因组的不到1%的物种中。 因此，搜索表明，这些蛋白质是罕见的，但分布很广。
研究人员选择了44种蛋白质进行无细胞表达测试，然后将主要考生移入E. coli. 24个考生中有15个生产可溶性蛋白，这15个考生中有7个在electron显微镜下形成库状颗粒。 Cryo-electron显微镜确认了其中4种的金库形状，其中2种来源于phages,2种来源于细菌。
费氏衍生的L05粒子被选作详细的结构分析，因为它是形成完整，闭合粒子的最佳粒子之一。 这一选择将项目从显微镜图像中检测出桶状物体到检查单个蛋白质链是如何组合在一起的，以及贝壳在哪里可以修改。
L05壳的工程
L05包含96份1个蛋白质，每半个排列为48份。 哺乳动物金库藏有78份，每半份有39份。 每个L05蛋白都有7个重复壁片段，而人类主要金库蛋白中有9个重复壁片段。 由此形成的壳体比人类的金库短，宽，但体积增加约25%.
其盖闭三步。 每组三个相邻蛋白质复制品中，一个在第一层结束，另一个在第二层结束，第三个在继续到尖端。 复制品沿墙面相同，但采用不同的配方，如盖子窄。
为了调查组装需要哪些联系人，小组做了15个修改后的L05版本，大部分是改变相邻副本触碰的点。 壁缝或顶盖附近的一些单置替代物产生开放的，类似玫瑰花状的粒子或聚合物，而不是封闭的金库，从而确定封壳所需的区域。
将两个壁段相重叠，使L05重复9次，并产生封闭颗粒，封闭体积增加约20%。 作者将此解读为重复复制可以不阻止组装而调整金库大小的证据，为大小可控纳米盖提供了可能的路径。 货物封装和交付是拟议的工程方向；证明的结果是对壳几何的控制。
Claude的作用和实验极限
研究人员自己选择了候选蛋白质。 Claude将所选择的蛋白质序列转化为适合其表达主机的DNA设计，增加了基因控制序列，并准备了订购的设计。
纯化提供了最明确的时间比较之一。 Anthropic 称其优化的大小排除色谱法将从细胞到显微镜网的行程缩短到约90分钟，而为eukaryotic金库开发的常规糖分法则大约为3天。 在缩放柱子时，颗粒过大，无法进入多孔的珠子首先出现，而较小的分子则延迟出现。
Claude最初反对这种方法，因为蛋白质总和可能在同样被排除的体积中出现。 它随后帮助推荐了一个柱子，追踪蛋白质和检查颗粒形成的方法，以及未经事先净化直接装入破裂细胞内装物。
对于结构处理，Claude在内部多agent带内运行，内部计算资源。 它建立并运行了开源RELION工作流程，同时研究人员指导了分析决策。 Anthropic报告说，第一个完整的模型在34小时后就已准备就绪，最后的地图在开始处理大约一周后就已准备好，同时估计最初的模型本来需要几周的时间。 该项目用了四个月。
包括Claude Science和Claude Code在内的各种Claude模型和界面，撰写了该研究的代码并进行了计算分析，由作者指导工作并接受内容责任。 Anthropic 称的大部分步骤可以由一个典型的实验室利用现有的Claude产品来进行，尽管平行的低温-EM分析使用了数百个超过许多学术机构可能拥有的GPU.
工作流程也产生了相应的错误。 一个Claude书面协议指定了一种生长介质添加剂，干扰了将DNA引入细胞，将项目延迟了两周。 早期的 cryo-EM 运行跳过一个标准步骤并生成了一个与其镜像混合的缺陷地图。 Anthropic与其模型训练研究者共享实验室指出，称之后的Claude模型似乎使DNA设计错误减少，并更有效地识别实验陷阱。
每份L05蛋白复制品还包含一个口袋，其密度未解决，来自一个不明的小分子。 技术报告描述了对25,000分子的计算搜索，将共环A或衍生物确定为候选的韧带。 分子的特性或任何功能影响都未得到证实。
迄今为止，这些粒子只在E. 大肠杆菌中产生，研究者没有测试它们是否在蛋白质自然发生的细菌和疟原虫中形成。 Anthropic向BioRxiv提交了技术报告，并计划日后发布结构和额外数据。
直接的推进是对蛋白质壳家族的实验性控制，这些蛋白质壳现在可以在细菌中产生，详细绘制，并通过重复复制来调整大小。 更大的问题仍然是生物学的：这个较简单的系统和不明的绳子是否能够帮助解释金库的作用，以及颗粒是否在其基因自然发生的生物体内组装。
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Anthropic Uses Claude to Show Bacterial and Phage Proteins Form Vaults
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Anthropic reported the results on November 4, 2026, showing that prokaryotic and bacteriophage relatives of the major vault protein can assemble into vault particles when produced in E. coli. Claude helped the team map one bacteriophage-derived shell at a nominal resolution of 3.2 angstroms.
Vaults are large, hollow protein shells whose biological function remains unknown. Producing related particles in bacteria gives researchers a faster-growing system for investigating their assembly, contents, and origins. Anthropic describes the L05 result as the first 3D structure of a vault particle found in prokaryotic cells. The work establishes assembly and architecture while leaving biological function unresolved.
From Protein Search to Confirmed Vaults
Using Claude Science, the researchers searched a database of approximately 15 billion predicted proteins. They found major vault protein homologs in 29 bacterial phyla and four archaeal phyla, although these proteins appeared in less than 1% of species with sequenced genomes. The search therefore showed that the proteins are rare but broadly distributed.
The researchers selected 44 proteins for cell-free expression testing before moving leading candidates into E. coli. Fifteen of 24 candidates produced soluble protein, and seven of those 15 formed vault-like particles under electron microscopy. Cryo-electron microscopy confirmed the vault shape in four of them, two derived from phages and two from bacteria.
The phage-derived L05 particle was selected for detailed structural analysis because it was among the best at forming complete, closed particles. That selection moved the project beyond detecting barrel-shaped objects in microscope images to examining how individual protein chains fit together and where the shell could be modified.
Engineering the L05 Shell
L05 contains 96 copies of one protein, arranged as 48 copies in each half. Mammalian vaults contain 78 copies, with 39 in each half. Each L05 protein has seven repeating wall segments, compared with nine in human major vault protein. The resulting shell is shorter and wider than the human vault but encloses approximately 25% more volume.
Its cap closes in three steps. Within each group of three neighboring protein copies, one ends at the first tier, another at the second, and the third continues to the tip. The copies are identical along the wall but adopt different conformations as the cap narrows.
To investigate which contacts are necessary for assembly, the team made 15 altered versions of L05, mostly changing points where neighboring copies touch. Some single substitutions near the wall seam or cap produced open, rosette-like particles or aggregates instead of closed vaults, identifying regions required to seal the shell.
Duplicating two wall segments gave L05 nine repeats and produced closed particles with approximately 20% more enclosed volume. The authors interpret this as evidence that repeat duplication can adjust vault size without preventing assembly, offering a possible route to size-tunable nanocapsules. Cargo encapsulation and delivery are proposed engineering directions; the demonstrated result is control over shell geometry.
Claude’s Role and the Experimental Limits
The researchers selected the candidate proteins themselves. Claude converted the chosen protein sequences into DNA designs tailored to their expression hosts, added gene-control sequences, and prepared the designs for ordering.
Purification provided one of the clearest time comparisons. Anthropic says its optimized size-exclusion chromatography method reduced the journey from cells to a microscopy grid to about 90 minutes, compared with approximately three days for the conventional sugar-gradient method developed for eukaryotic vaults. In sizing columns, particles too large to enter the porous beads emerge first, while smaller molecules are delayed.
Claude initially argued against that approach because protein aggregates could emerge in the same excluded volume. It subsequently helped recommend a column, methods for tracking the protein and checking particle formation, and the direct loading of ruptured-cell contents without prior purification.
For structural processing, Claude operated inside an internal multi-agent harness with internal computing resources. It set up and ran the open-source RELION workflow while researchers guided the analytical decisions. Anthropic reports that a first full model was ready after 34 hours and final maps about a week after processing began, while estimating that an initial model would otherwise have taken weeks. The project took under four months.
Various Claude models and interfaces, including Claude Science and Claude Code, wrote the study’s code and performed its computational analyses, with the authors directing the work and accepting responsibility for the content. Anthropic says most steps could be performed by a typical laboratory using existing Claude products, although the parallel cryo-EM analysis used hundreds of GPUs beyond what many academic institutions may have available.
The workflow also produced consequential errors. One Claude-written protocol specified a growth-medium additive that interfered with introducing DNA into cells, delaying the project by two weeks. An early cryo-EM run skipped a standard step and generated a flawed map blended with its mirror image. Anthropic shared the laboratory notes with its model-training researchers and says subsequent Claude models appeared to make fewer DNA-design errors and identify experimental pitfalls more effectively.
Each L05 protein copy also contains a pocket with unresolved density from an unidentified small molecule. The technical report describes a computational search of 25,000 molecules that identified coenzyme A or a derivative as a candidate ligand. Neither the molecule’s identity nor any functional implication has been confirmed.
The particles have so far been produced only in E. coli, and the researchers have not tested whether they form in the bacteria and phages where the proteins naturally occur. Anthropic has submitted the technical report to bioRxiv and plans to release the structures and additional data later.
The immediate advance is experimental control over a family of protein shells that can now be produced in bacteria, mapped in detail, and resized through repeat duplication. The larger question remains biological: whether that simpler system and the unidentified ligand can help explain what vaults do, and whether the particles assemble in the organisms where their genes naturally occur.
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