The problem of growing protein crystals with sufficiently high resolution for accurate structure determinations is so important that it has justified a major NASA program to grow protein crystals in microgravity. About 25% of the microgravity-grown crystals show significant improvement in resolution, apparently because of the inhibition of solute transport by the suppression of buoyant convection. conversely, the perfection and resolution of the other 75% could, according to the analysis of Rosenberger and Velikov, be improved by the enhancement of solute transport, e.g. by stirring. However, the first approach is too expensive for extensive application and the second too prone to instabilities for reliable growth optimization. We therefore propose to optimize the resolution quality of all classes of protein crystals by using new growth techniques to adjust the transport of solute to suit the growing crystal.
Our specific aims are (1) to improve the resolution of some protein crystals by achieving the transport- retarding advantages of microgravity in low-cost ground-based convectionless experiments and (2) to improve the resolution of other protein crystals by growth in transport-enhancing centrifugal fields. We propose. to demonstrate feasibility during Phase l and develop wide- spread use and commercialization during Phase Il.
If successful, this project would facilitate high-throughput structure determinations of proteins, thereby creating a market among structure biologists for the apparatus developed and/or helping to create a new service industry of protein crystal growth and structure determination. Although the revenues thus generated would be comparatively modest, the indirect revenues, i.e. the overall value to the biomedical community, would be far greater.
