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Home | DTI | 2005–06 funded proposals | Victor H. Barocas, Jeffrey Jay Derby, Jennifer A. Maynard, Caroline M. Wilmot, Paul W. Todd

Initiatives in Digital Technology: 2005–06 Funded Proposals

Victor H. Barocas, Jeffrey Jay Derby, Jennifer A. Maynard, Caroline M. Wilmot, Paul W. Todd

Computer-Aided Protein Crystallization Design: X-ray crystallography is the tool of choice for structural analysis of biomacromolecules, especially proteins.

X-ray crystallography is the tool of choice for structural analysis of biomacromolecules, especially proteins. At present, the critical and most challenging step in the analytical process is creating a crystal of sufficient size and quality for crystallography to be performed. The most common approach to crystal growth is the so-called "high throughput" strategy, which involves trying as many crystallization protocols as possible in the hope of producing a good crystal. If feasible, a rational approach would obviously be preferred. We propose to develop a multiscale model of protein crystallization in a novel continuous-feed crystallization microdevice being developed by Barocas and Todd. The model will couple a continuum-level transport with mesoscale transport and crystal growth, accounting for the possibility of multiple crystals forming in the same crystallizer. We will also consider the prospect of an applied electric field, which has been shown to improve crystallization in some cases, and manipulation of the protein dipole moment, which is now possible via protein engineering. Our objective is to create a computeraided crystallization design tool that will advise the structural biologist on the appropriate operating conditions √¢eed concentrations, feed rates, operation time, and electric field √¢o maximize the likelihood of growing a high-quality crystal from a native or an engineered protein. Although the goal of this short-term project is only a basic tool with emphasis on proteins, our longer-term goal is to develop a general tool for all biomacromolecules that could account for constraints as a finite amount of available material or a maximum allowable flow rate.