PanDDA analysis of DCP2B screened against DSPL/DSi Poised, OxXChem fragment libraries and initial follow up chemistry

<strong>SGC Oxford has performed a crystallographic fragment screen, and initial follow up chemistry on the </strong><strong>Human m7GpppN-mRNA Hydrolase (DCP2/NUDT20, UniProtKB - QIU60). All structures with clearly identifiable ligands were deposited in the Protein Data Bank under Group Deposition ID G_1002061, the corresponding apo structures are deposited under Group Deposition ID G_1002062. </strong> <em><strong>Experiment</strong></em> Crystals were prepared at the XChem facility of the Diamond Light Source (DLS). Briefly, crystals were soaked overnight with two fragment libraries; the Diamond- SGC Poised Library set (Cox et al., 2016) and the OxXChem set with nominal fragment concentrations of 100 mM, with DMSO at 20% v/v. Additionally, a series of follow-up compounds based on an initial fragment hit was synthesized and soaked overnight with nominal compound concentrations of 10-200 mM, with DMSO at 20% v/v. All datasets were collected at MX beamlines at DLS. Autoprocessed datasets were analysed by Pan-Dataset Density Analysis (PanDDA) (Pearce et al., 2017). All ligands that were clearly identifiable in PanDDA event maps were modelled, refined and deposited into the PDB. <em><strong>Content</strong></em> This repository contains: <em><strong>Modelled Data</strong></em> Organised by crystal identifier, each folder contains: Autoprocessing data from Diamond Light Source automated pipelines (including MTZ) PDB, CIF &amp; PNG files of all the soaked compounds PanDDA event maps Final refine.pdb and refine.mtz files of all ligand bound structure Superposed structures (refine.pdb) Separated bound &amp; ground states (refine.split.bound.pdb &amp; refine.split.ground.pdb) <em><strong>PanDDA Analysis Data</strong></em> This is split into two directories. This split is only due to technical limitations at the time of preparation of the data, and the timeliness of the data. All results from the PanDDA analysis, including ground-state-mean maps and PanDDA event &amp; Z-maps for all ligand bound structures.**结构基因组学联盟（Structural Genomics Consortium, SGC）牛津分部**已针对人类m7GpppN mRNA水解酶（Human m7GpppN-mRNA Hydrolase, DCP2/NUDT20, UniProtKB - QIU60）完成了晶体学片段筛选及初步后续化学衍生研究。所有带有可明确识别配体的晶体结构已以群组提交编号G_1002061提交至蛋白质数据库（Protein Data Bank, PDB），对应的无配体（apo）结构则以群组提交编号G_1002062完成提交。 **实验方法** 晶体制备工作在钻石光源（Diamond Light Source, DLS）的XChem实验站完成。简言之，晶体先后经两种片段文库浸泡过夜：分别为Diamond-SGC预优化文库（Diamond-SGC Poised Library set, Cox等, 2016）与OxXChem文库，片段终浓度标称值为100 mM，二甲基亚砜（Dimethyl Sulfoxide, DMSO）体积占比为20% v/v。此外，研究团队基于初始片段命中物合成了一系列后续衍生化合物，并以标称浓度10~200 mM将其与晶体共孵育过夜，体系中二甲基亚砜体积占比同样为20% v/v。所有衍射数据集均于DLS的MX光束线站采集。经自动处理的衍射数据集通过全数据集密度分析（Pan-Dataset Density Analysis, PanDDA, Pearce等, 2017）进行解析。所有可在PanDDA事件图中明确识别的配体均已完成建模、精修，并提交至PDB。 **数据集内容** ***建模数据*** 本数据集按晶体标识符进行分类，每个子文件夹包含以下内容： 钻石光源自动化数据处理流程产出的自动处理数据（含MTZ格式文件） 所有浸泡实验所用化合物的PDB、晶体学信息文件（CIF）及便携式网络图形（PNG）文件 PanDDA事件图 所有配体结合结构的最终精修文件refine.pdb与refine.mtz： 叠加后的结构文件（refine.pdb） 分离的结合态与基态结构文件（refine.split.bound.pdb与refine.split.ground.pdb） ***PanDDA分析数据*** 该数据分为两个子目录，此次拆分仅源于数据制备当时的技术限制及数据时效性要求。 所有配体结合结构的PanDDA分析结果，其中包括基态平均图以及PanDDA事件图与Z值图。