W0094

Protocol Development for High Throughput Crystallography. I. Mochalkin¹, A. Aleshin¹, J. Bell¹, F. Hernandez¹, F. Gliubich², D. Kitson¹, S. Szalma¹, D. Edwards¹, and R. Hubbard², ¹ Accelrys Inc. 9685 Scranton Rd., San Diego, CA 92121-3752, USA, ²Accelrys Ltd. Dept. of Chemistry, Univ. of York, Heslington, York, UK.

High-throughput crystallography faces two challenges in terms of software and informatics support. The first is the development of automated protocols for all stages of the structure determination process; the second is providing the informatics environment that will track the progress of structure determination and provide links to chemical and biological data.

In this presentation, we describe protocols and the results of validation studies to develop a fully automated approach for solving protein structures by molecular replacement using a set of homologous models and the corresponding sequence alignments. The protocols encompass algorithms for initial structure editing, molecular replacement and iterative model building using real and reciprocal space refinement integrated with the validation of protein geometry and structure fit to electron density. The approach has been tested on more than 20 protein systems with sequence identity between the search model and target of 40 % or higher and with the insertions up to 6 residues long. The progress of calculations and the related data generated during the structure determination process are automatically tracked within Accelrys’ Discovery Studio infrastructure. These data can be linked to different databases and easily and instantly shared between department members working on the same project.