Department of Biochemistry, Machine VP
University of Sydney
Structure Refinement and Molecular Calculations for Proteins
Knowledge of the three-dimensional structures of biologically active macromolecules is commonly believed to be necessary prerequisite for a full understanding of the function of the molecule. For large molecules (those in excess of 25,000 Da molecular weight), structures are most commonly obtained using single crystal X-ray diffraction methods. Optimisation of these structures is performed using molecular dynamics and simulated annealing calculations, involving thousands of variables and tens of thousands of observations. These calculations are greatly speeded up on a supercomputer.
What are the basic questions addressed?
The structures of a number of proteins, including copper-containing amine oxidases, ATPase subunits and glycosaminoglycan degrading enzymes.
What are the results to date and the future of the work?
The molecular dynamics program X-PLOR was successfully ported to the VP2200. The FFT routines were optimised for the vector processor. We refined the structure of a small blue copper protein. The other projects are currently at an early stage in the structure analyses and do not yet require molecular dynamics. The projects at the refinement stage are small proteins and are more easily handled by in-house workstations.
What computational techniques are used and why is a supercomputer required?
The calculations comprise molecular mechanics and dynamics on proteins restrained by X-ray diffraction observations. The time consuming steps are large three dimensional Fourier transforms and the matrix operations involved in the minimisation procedures. The increasing speed of stand-alone workstations has for the moment removed any advantage obtained from the supercomputer. This may change with the size of problems being tackled and any upgrades that are made to the VP2200.