Lead Chief Investigator

Jill E Gready Computational Proteomics, JCSMR, Australian National University

Project Title

Simulation of Protein Properties; Conformations of Disordered Peptides

Brief Description for General Publications

A rich opportunity for simulation is definition of the conformational manifold of disordered peptides. Whole-genome analyses show sequence regions of proteins likely to be structurally disordered constitute ~10% of proteomes, but they have been little characterized so far. Our work in this area, using a combined computational and experimental approach, is focussed on prion protein (PrP) and its homologue Shadoo (Sho), newly discovered by us. We are investigating the conformational distributions of the N-terminal repeat regions of PrP and Sho and the possibility that they may form transient sub-structures. We use MD simulations implemented within the efficiently parallelized replica-exchange molecular dynamics (REMD) method and also a more recent refinement, hybrid-solvation REMD (HS-REMD), which allows a more efficient treatment of solvation.