New Tools for Experimental Phasing of Twinned Diffraction Data

摘要 结晶学是现代结构生物学中不可或缺的工具，允许精确地 蛋白质中分子相互作用的测定。大部分计算量 现有的结晶学工具是在衍射数据的前提下开发出来的 没有像双胞胎这样的病态。用于双生数据的检测和精化 结构，已经有了优秀的软件，但对于更上游的任务，没有通用的- 有专门的工具可用。缺少允许处理双胞胎数据的工具 在从这样的数据求解结构时遇到实际困难。这项提议解决了这个问题 通过为所有主流开发结对感知工具和算法来实现关键差距 不存在此类工具的结晶学任务。我们建议采用和扩展现有的 密度修正和重原子测定方法，使其适用于 处理双胞胎数据。所提出的算法从实数中传播重要的先验信息 空间一直到数据空间，在数值上稳定了原本病态的去孪生 步骤使用正则化方法。为社区提供一整套工具 对于从头分阶段，重原子精化和分阶段战略将通过 发展和评估孪生SAD似然法所需的数值技术 功能。这个问题将使用自适应求积方法来解决。

Summary Crystallography is an indispensable tool in modern structural biology, allowing for precise determination of molecular interactions in proteins. The majority of the computational crystallographic tools available have been developed on the prerequisite that the diffraction data is free from pathologies such as twinning. For the detection of twinned data and refinement of structures, excellent software is already available, but for more upstream tasks, no general‐ purpose tools are available. The absence of tools that allow handling of twinned data has resulted in practical difficulties when solving structures from such data. This proposal addresses this critical gap by developing twinning‐aware tools and algorithms for all mainstream crystallographic tasks for which no such tools exist. We propose to adopt and extend existing density modification and heavy atom determination methods such that they are suited for handling twinned data. The proposed algorithm propagates vital prior information from real space all the way into data space, numerically stabilizing an otherwise ill‐conditioned detwinning step using a regularization approach. To provide the community with a full complement of tools for de novo phasing, heavy atom refinement and phasing strategies will be addressed by developing and evaluating numerical techniques needed for the twinned‐SAD likelihood function. This problem will be addressed using an adaptive quadrature approach.