Structure and dynamics of Escherichia coli adenylate kinase
Berry, Michael Brandon
Phillips, George N., Jr.
Doctor of Philosophy
Escherichia coli adenylate kinase has been studied by X-ray crystallographic and molecular dynamics approaches. The structures of E. coli adenylate kinase complexed with either AMP and AMPPNP, or AMP and ADP are presented. The AMP/AMPPNP complex has been determined to a resolution of 2.0 A, and confirms the location of the AMP and ATP binding sites on the protein. The AMP/ADP complex has been determined to resolution of 2.8 A, and demonstrates the geometry of this inhibitory complex. Molecular dynamics studies of E. coli adenylate kinase have been done using the weighted masses technique. Simulations were conducted using two general protocols (CHARMM and X-PLOR) which differ in the nature of the secondary structural constraints applied. Both protocols were successful in simulating the opening of the two mobile domains of the protein. The X-PLOR based trajectories, using a heterogeneous weighting system, were also able to simulate the closing of the mobile domains, resulting in a more Gaussian distribution of conformations than that seen in the CHARMM based method.