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.
The role of structural biology in facilitating an understanding of biological function is well established, and advances in crystallization methods will assist researchers in overcoming crystallization as a major source of attrition in their investigative pipelines. Improvements in protein crystallization outcomes will positively impact productivity in structural biology, with Public Health benefits accruing from faster knowledge acquisition and more efficient drug development.
| Nordquist, Kyle A; Schaab, Kevin M; Sha, Jierui et al. (2017) Crystal Nucleation Using Surface-Energy-Modified Glass Substrates. Cryst Growth Des 17:4049-4055 |
