RAPPER Nick Furnham Blundell Group – Department of Biochemistry Cambridge University UK

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Presentation transcript:

RAPPER Nick Furnham Blundell Group – Department of Biochemistry Cambridge University UK

RAMPAGE Tool for generating Ramachandran plots for structure validation. Stripped out of RAPPER. Defined file structure (will use as basis for RAPPER) in CCP4 main distribution. Have autoconf build working (thanks Charles). Have windows build (thanks Francois). Have replaced the Ramachandran plot from Procheck in validation CCP4i window (thanks Peter and Martyn)

RAMPAGE

Sampling Major degrees of freedom are from the φ / ψ / ω. As sampling is a cpu intensive procedure only consider φ / ψ fix ω to 0 or 180 Use fine-grained residue specific φ/ψ state sets. Also sample side chain rotamers from a detained hand-curated side chain conformation libraries

Constraint & Restraint When searching optimising on: Implicit Constraints: Ideal Engh & Huber stereochemistry Van der Waals overlaps: Efficiently checked for by a grid based cache Arbitrary Restraints: Positional restraints Experimental Data e.g. X-ray electron density Framework restraints Secondary Structure

Sampling

RAPPER By going through the process with RAMPAGE now have bases for integrating RAPPER. Latest development has been to bug fixed and extended to cope with SeMet (modelling and accounting for heavy atom scattering) and other heavy atom scatters in internal map calculations. Now have a frozen working development. Have a 32bit Linux distribtion but problems in transporting to 64bit (int casting issues) Can force through compiler but is this cross platform solution – any ideas?

RAPPER How to integrate into suite – what functionality is best to concentrate on? We would like to start with loop generation given weak density. Can also have multi-model ensemble generation using automated rebuilding and refinement or rebuilding entire structure or low resolution hypothesis testing

RAPPER Research directions: –Multi model conformations for multimeric structures to study heterogeneity and uncertainty in protein-protein interfaces. –Resolving CASP targets from CASP7 –In discussion with Garib about using RAPPER to provide a ‘bootstrap’ map. –Now have developed RAPPERtk - an extrapolation of RAPPER to allow extension to modelling strategies. Now includes RNA / DNA conformer modelling EM envelope fitting Ligand modelling Nearly can cope with NMR data!