title: Rapid shape determination of tissue transglutaminase using high-throughput computing.
abstract: Small-angle X-ray scattering can be used to determine the molecular shape of macromolecules in solution which are otherwise refractory to conventional high-resolution studies. DAMMIN and GASBOR are applications that utilize ab initio methods to build models of proteins using simulated annealing; both DAMMIN and GASBOR have to be run numerous times on the same input data to generate the most likely protein shape. Condor is a specialized workload-management system for PC computation-intensive tasks. Using Condor, DAMMIN and GASBOR can be run a number of times simultaneously on the same input data, allowing the shape of proteins to be determined in a fraction of the time it would have taken to have run DAMMIN and GASBOR sequentially. The main advantage of this approach is that it allows quicker data processing; therefore, results are obtained promptly and without undue delay. Tissue transglutaminase is a multidomain enzyme that catalyses the formation of isopeptide bonds between polypeptide chains. This reaction requires the enzyme to undergo a series of conformational changes that are not well understood in order to allow the sequential interaction with the two substrate proteins and their subsequent release when cross-linked. Condor was applied to determine the solution shape of tissue transglutaminase in a rapid fashion. Eventually, the next step will be to move towards online analysis at synchrotron sources by developing a graphical user interface that will enable remote access, allowing users to submit jobs to Condor whilst at synchrotrons.
authors: School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4LU, Wales. lammied@cf.ac.uk
authors: Donna
authors: D
authors: Lammie
authors: James
authors: J
authors: Osborne
authors: Daniel
authors: D
authors: Aeschlimann
authors: Timothy J
authors: TJ
authors: Wess
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011503:Transglutaminases / Q000737:chemistry*
chemical_list: D011506:Proteins; D011503:Transglutaminases