Microdomain Thermal Perturbations for Enhanced Nucleation of Proteins

 描述（由申请人提供）：结晶蛋白质用于结构生物学的能力仍然非常具有挑战性，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，以提高蛋白质和小分子药物结晶的成功率和重现性。DeNovX有两种互补的平台技术用于改善晶体成核，这些产品与微区热处理的结合是一种创新和有前途的蛋白质方法，因为微区强调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来提高材料结晶的成功率 这与从结构生物学到新药开发的研究领域广泛相关。我们建议，模型蛋白质的成核可以重复加速，使结晶材料，通过使用微域热处理在接近专门设计的成核表面。第二阶段的开发将针对更多样化的蛋白质，包括难以结晶且与公共卫生高度相关的GPCR。DeNovX的互补技术用于创建定制的成核表面，再加上创新的热处理，将成为高价值耗材产品线的基础。

 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.