Microdomain Thermal Perturbations for Enhanced Nucleation of Proteins

微域热扰动增强蛋白质成核

• 批准号: 8833846
• 负责人: Andrew H. Bond
• 金额: $ 22.39万
• 依托单位: DENOVX, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-10 至 2016-07-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833846
• 关键词: Acceleration; Affect; Area; Biological Process; Biological Sciences; Cattle; Characteristics; Chemicals; Complement; Coupled; Crystallization; Crystallography; Data; Development; Engineering; Goals; Grant; Growth; Health Benefit; Institutes; Investments; Knowledge acquisition; Laboratories; Legal patent; Licensing; Liquid substance; Methods; Modeling; Modification; Outcome; Pancreas; Pharmacologic Substance; Phase; Process; Productivity; Proteins; Public Health; Reproducibility; Research; Research Personnel; Resolution; Role; Sampling; Services; Solubility; Solutions; Source; Stream; Structural Biologist; Structure; Surface; Techniques; Technology; Time; Trypsin; Wettability; base; commercial application; design; drug development; high throughput screening; improved; innovation; monolayer; professor; public health relevance; small molecule; structural biology; success; technological innovation; tool

 DESCRIPTION (provided by applicant): The ability to crystallize proteins for structural biology remains quite challenging, with realized protein crystallization/structure determination success rates hovering around 3%. DeNovX is developing rationally designed nucleation surfaces and thermal methods that enhance success rates and reproducibility for crystallization of proteins and small molecule pharmaceuticals. DeNovX has two complementary platform technologies for improving crystal nucleation, and the combination of these products with micro domain thermal treatment is an innovative and promising approach for proteins, as the micro domain emphasis overcomes protein solubility and stability issues that may adversely affect bulk thermal methods. The long-term goal of this effort is to develop tools to improve success in crystallizing materials that are broadly relevant to research areas ranging from structural biology to new pharmaceutical development. We propose that nucleation of model proteins can be reproducibly accelerated to give crystalline materials by using micro domain thermal treatment in proximity to specially engineered nucleation surfaces. Phase II development will target more diverse proteins including the GPCR's that are both difficult to crystallize and highly relevant to Public Health. DeNovX's complementary technologies for creating tailored nucleation surfaces coupled with innovative thermal treatments will be the basis of a high value consumables product line.

 描述（由申请人提供）：用于结构生物学的蛋白质结晶能力仍然相当具有挑战性，实现的蛋白质结晶/结构测定成功率徘徊在 3% 左右，DeNovX 正在开发合理设计的成核表面和热方法，以提高成功率和重现性。 DeNovX 拥有两种用于改善晶体成核的互补平台技术，这些产品与微域热处理的结合是一种创新且有前途的方法。对于蛋白质，因为微域重点克服了可能对批量热方法产生不利影响的蛋白质溶解度和稳定性问题。这项工作的长期目标是开发工具以提高结晶材料的成功率。 我们提出，通过在专门设计的成核表面附近使用微域热处理，可以可重复地加速模型蛋白质的成核，从而产生结晶材料。更多样化的蛋白质，包括难以结晶且与公共健康高度相关的 GPCR，用于创建定制成核表面的补充技术加上创新的热处理将成为高价值的基础。耗材产品线。