W0293

QUANTA: Automated Electron Density Maps Interpretation, Model Building and Structure Validation. Andrew English¹, Igor Mochalkin², Francesca Gliubich³, Mary Donlan⁴and Tom Oldfield⁵, Molecular Simulations Inc., ¹200 Wheeler Road, South Tower, 2nd Floor, Burlington, MA 01803-5501, USA, ²9685 Scranton Road, San Diego, CA 92121-3752, USA, ³230/250 The Quorum, Barnwell Road, Cambridge Cambs CB5 8RE, UK, ⁴Parc Club Orsay Université, 20, rue Jean Rostand, F-91893, Orsay Cedex, France, ⁵Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.

Recent advances and developments in genomic, molecular and crystallographic data analysis and techniques has generated a huge need to develop new tools and methods to manage databases containing structural and functional information, as well as accelerate and automate protein structure determination. The latter is especially important in at the rate limiting stages de novo map interpretation and protein model building. In order to meet this demand, the most recent developments in the QUANTA software package target automation as one of the most desired techniques for protein crystallographers to accelerate de novo map interpretation, model building and structure validation.

Interpretation of the electron density map in QUANTA includes: (1) “bones” skeletonization of the electron density; (2) vector analysis; (3) map tracing and (4) automated sequence assignment. Recent improvements in the vector analysis provide a more robust algorithm implemented in the X-POWERFIT module to cluster vectors and check for protein secondary structure motifs, such as (-sheets and (-helices. The tracing method has been automated to the level at which it can trace C-( atoms of an entire structure of a medium size protein with a single button press. Automated sequence assignment is based on the comparison of aromatic patterns in the electron density with those in the sequence. QUANTA provides modules for automated model building, structure refinement, automated ligand fitting to electron density and validation. QUANTA also includes an interface to features of the CNX program for crystallographic calculations.

This technology has been developed in close collaboration with crystallographers at the University of York and Molecular Simulations Inc.