Computational methodology for macromolecular crystallography. (360G-Wellcome-064405_Z_01_A)

My research proposal is to continue the development and application of advanced statistical, computational-chemical techniques for macromolecular crystal structure analysis and to extend this research towards other fields ofstructural biology. It has several interlinked, but at the same time independent key goals: (1) Organisation of a database encapsulating the knowledge available in the Protein Data Bank in a usable form for Macromolecular crystallography (2) Automated molecular replacement to integrate this database with software developed in my group, employing statistically robust decision making procedures (3) Improved electron density calculation after refinement by transferring information from the experimentaldata and database of structural features to newly solved structures (4) Completing the structure using knowledge from chemistry, physics and macromolecular structures (5) Optimal fit of an MX model into EM density usingmaximum likelihood combined with prior structural knowledge (6) Ligands and their geometry, quantum chemical optimisation of the geometry of the building blocks of macromolecules and ligands (7) Application of the techniques developed to difficult problems and exploiting feedback from experimenters. The software developed will be made available to the structural biology community via the UK based initiative, CCP4