National HTX Center: Enabling Access to State-of-the-Art Crystallization Capabilities

国家 HTX 中心：获得最先进的结晶能力

基本信息

批准号：
10798961
负责人：
Sarah Elizabeth Johnson Bowman
金额：
$ 20万
依托单位：
HAUPTMAN-WOODWARD MEDICAL RESEARCH INST
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

项目摘要

PROJECT SUMMARY Structural biology is a field with a goal to delineate the physical architecture of biological macromolecules; a primary structural method employed in this endeavor is macromolecular X- ray crystallography (MX). MX methods account for nearly 90% of the greater than 165,000 structures deposited to the Protein Data Bank, but a primary challenge to successful MX structure determination is finding conditions in which a macromolecule will crystallize. To address this obstacle, an arsenal of chemical cocktail screens and high-throughput screening methods, coupled with specialized imaging, have been brought to bear on the problem of determining the conditions in which a macromolecular target will form a crystal that is of sufficient quality to be amenable to X-ray diffraction structure determination. This proposal focuses on continuing and extending the capabilities of a central resource providing critical high-throughput crystallization screening to the scientific community, the High-Throughput Crystallization Screening Center (HTX) at Hauptman-Woodward Medical Research Institute. The HTX Center has been in operation for two decades, providing a unique national crystallization resource specifically geared to help overcome the obstacle of coaxing a macromolecule to crystallize. The HTX Center provides a high-throughput screening format designed to minimize sample requirements via use of small volume liquid-handling robotics, a unique experimental set-up, and state-of-the-art imaging for screening. Notably, the technologies, instruments, and expertise available at the HTX Center are not widely available. This proposal focuses on extending the capabilities of the HTX Center by developing an expanded repertoire of experimental screening options and improved image analysis and processing, while performing instrumentation upgrades to maintain the HTX Center as a premier resource for crystallization screening for the scientific user community. We propose developing and implementing the necessary computational infrastructure and software to accommodate new screening plate definitions and optimization of successful crystallization hits, and improved user interfaces to maximize the information accessibility from screening experiment outcomes. A major goal of this proposal is to increase access to the state-of-the-art crystallization screening instrumentation and expertise to researchers from a wide array of laboratories in academic, non-profit and government institutes, with an objective to ensure access that enables a broad range of biomedically important research.

项目摘要结构生物学是一个目标，目的是描述生物学的物理结构大分子；这项工作中采用的主要结构方法是大分子x- 射线晶体学（MX）。 MX方法占大于165,000的近90％沉积在蛋白质数据库中的结构，但对成功MX结构的主要挑战确定是发现大分子将结晶的条件。解决这个问题障碍物，化学鸡尾酒屏幕和高通量筛查方法的武器库，再加上专业成像，已经确定了确定的问题大分子目标将形成足够质量的晶体的条件适合X射线衍射结构的确定。该提案的重点是继续和扩展中央资源的功能，提供关键的高通量结晶筛选科学界，高通量结晶筛选中心（HTX）在Hauptman-Woodward医学研究所。 HTX中心已经进入运营已有二十年，提供了独特的国家结晶资源专门配备帮助克服哄骗大分子结晶的障碍。 HTX中心提供高通量筛选格式，旨在通过使用最小化样本要求小型液体处理机器人技术，独特的实验设置和最新的成像进行筛选。值得注意的是，HTX提供的技术，工具和专业知识中心不是广泛可用的。该建议重点是扩展HTX的功能通过开发扩展的实验筛选选项的曲目并改进图像分析和处理，同时执行仪器升级以维护HTX 中心是科学用户社区结晶筛查的主要资源。我们建议开发和实施必要的计算基础架构和软件为了适应新的筛选板定义和成功结晶的优化点击并改进了用户界面，以最大化筛选的信息可访问性实验结果。该提案的主要目标是增加对最先进的访问权限从各种各样学术，非营利和政府机构的实验室，以确保进入这样可以进行广泛的生物医学重要研究。