W0274

DS HT-XMR: A New Application in Discovery Studio Modeling for Automatic Structure Solution by Molecular Replacement Method. Alexander E. Aleshin, Jeff Bell, Alan Burye, David Kitson, Igor Mochalkin, and Rod Hubbard^#, Accelrys Inc., 9685 Scranton Rd., San Diego, CA 92121, USA, ^#Accelrys LTD., Univ. of York, YO10 5DD, UK.

With the increasing number of determined protein structures molecular replacement has become a very attractive approach for solving new structures. It requires neither heavy-atom modification of proteins, nor synchrotron data collection. Homologous structures are also very useful during the model building process. Utilization of the method for automatic structure solution, however, is not a trivial task because of bias and the poor quality of difference Fourier maps in areas requiring rebuilding. Homologous structures also may have internal errors, which are difficult to detect and fix. This presentation will describe our attempts to address these and several other aspects of automatic structure solution by molecular replacement, implemented in a new Discovery Studio Module HT-XMR. HT-XMR combines molecular replacement search, reciprocal space refinement, model rebuilding, and structure validation into a single pipeline. It allows screening of different models and space groups during the search and automatic re-adjustment of the search algorithm if the initial trial fails. Sequence alignment, electron density correlation, and geometry violations are used for selecting residues to be rebuilt according to the omit maps.

The results of validation studies will be presented and discussed.