Structural Biology Core

有效的结构支持，周转时间短， 注释良好的结构数据的快速传播对命中到引导提供了显著影响， 领先的优化流程。钻石光源的贡献就是一个例证， COVID Moonshot -一项开放式科学合作，开发了一种新型非肽模拟小分子， 一种口服生物可利用的SARS-CoV-2主要病毒蛋白酶（Mpro）抑制剂，具有强效抗病毒作用 在不到12个月的时间内从高通量片段筛选开始。这个项目 证明了实现结构数据的实时周转不仅在技术上是可行的， 在科学上对加速复合进展至关重要。 此外，晶体学片段筛选是一种经过充分验证的蛋白质配体作图方法 结合位点，并确定开发新的治疗方法的起点， 疾病。这种技术是高度敏感的，由于同步加速器技术的发展， 再加上建立专门的筛选设施，如世界上第一个XChem平台， 钻石光源，现在的吞吐量与其他生物物理技术，如核磁共振 和SPR的优点是结构信息可以立即用于驱动片段到头部 发展 结构生物学核心已经专门位于钻石光源的XChem 利用其世界领先的高通量晶体学能力， 实施所需的物流和技术，以持续实现所需的加速， 实现ASAP AViDD中心雄心勃勃的药物化学目标。 这个核心将负责成功交付晶体碎片筛选，快速 由该中心产生的所有化合物的蛋白质-配体晶体结构的转变，并确保 所有的晶体结构都可以在公共领域以高质量和充分注释的方式迅速获得。

Effective structural enablement with short turn-around and rapid dissemination of well annotated structural data provides significant impact to the hit-to-lead and lead optimization processes. This has been exemplified by the contribution of Diamond Light Source to the COVID Moonshot - an open science collaboration that developed a novel non-peptidomimetic small molecule orally bioavailable SARS-CoV-2 main viral protease (Mpro) inhibitor with potent antiviral activity starting from a high-throughput fragment screen in less than 12 months. This project has demonstrated that achieving real-time turnaround of structural data is not only technically feasible, but scientifically crucial to accelerating compound progression. Additionally, crystallographic fragment screening is a well-validated method for mapping protein ligand binding sites and identifying starting points for the development of novel therapeutics for a wide range of diseases. This technique is highly sensitive and owing to developments in synchrotron technology plus the establishment of dedicated screening facilities, such as the world-first XChem platform at Diamond Light Source, the throughput is now comparable to other biophysical techniques such as NMR and SPR with the advantage that structural information is immediately available to drive fragment-tolead development. The Structural Biology Core has been specifically situated at the Diamond Light Source's XChem facility to capitalize on its world-leading high-throughput crystallography capabilities in order to implement the logistics and technologies required to consistently achieve the acceleration required to meet the ASAP AViDD Center's ambitious medicinal chemistry goals. This core will be responsible for the successful delivery of crystallographic fragment screens, the rapid turn-around of protein-ligand crystal structures for all compounds generated by this center and ensuring all crystal structures are promptly available, at high quality and fully annotated, in the public domain.