Significance: The most common method in the structure determination of proteins using x-ray crystallography is Molecular Replacement (MR), which relies on structural information from proteins that share sequence similarity with the target protein. However, MR is non-trivial when the sequence similarity is less than 30%, and the selection of a suitable starting model is difficult due to inherent model error. We have developed a method, employing objective pruning of multiply aligned structures, that produces superior candidate models for structure elucidation. We aim to build a web-based system that will leverage distributed computational resources to use these models to solve crystal structures in a high-throughput fashion.

Outcomes: A major new tool to solve the three-dimensional structures of proteins in a significantly shorter timeframe than is currently possible.

This project is in collaboration with colleagues at Monash University (Dr. Ashley Buckle and Dr. James C. Whisstock) and Univeristy of Melbourne( Prof. Peter J. Stuckey). I serve as a co-chief investigator. The project is funded by Victorian Partnership for Advanced Computing (VPAC), Australia.