Project overview
The way in which proteins move and flex is critical for their function. Unfortunately, the main experimental method for probing and determining protein structure, X-ray diffraction, provides comparatively little information on how the protein moves. Molecular dynamics computer simulations, on the other hand, are able to yield detailed information on protein dynamics that is very useful, particularly for rational drug design. In this proposal, large-scale high-performance computers will be used to simulate the dynamics of a broad range of the most important protein shapes, or folds. Studies of how specific mutations (for example, drug resistant mutations) affect the protein motions will also be performed. These simulations will take place as part of the SuperComputing 2005 scientific meeting, to demonstrate the power and importance of integrating large computing resources. Computer software to control the simulations, store their output, analyse and present the results, and select new simulations to be run, will be demonstrated. These studies are important not only for the computing community itself, but are also particularly timely because of recent development in protein X-ray structure determination. With the arrival of the Diamond Light Source in 2007, and the stated aims of the UK Structural Genomics Consortium (www.sgc.ox.ac.uk), the number of new protein structures available will increase significantly. This proposal will demonstrate how simulations may be directly linked to this experimental information, providing critical extra data on the protein dynamics.
