NUCLEOTIDE-BINDING PROPERTIES OF ADENYLATE KINASE FROM ESCHERICHIA-COLI - A MOLECULAR-DYNAMICS STUDY IN AQUEOUS AND VACUUM ENVIRONMENTS

The complex of adenylate kinase with its transition-state inhibitor ha s been studied by molecular dynamics simulations in water and in vacuu m environments with the GROMOS force field over a period of 300 ps. Th e adenylate kinase, a member of the nucleotide-binding protein family, was exemplarily chosen for the inspection of the nucleotide-binding p roperties in the active site. The ligand binding and the domain moveme nts have been studied in detail over the simulation period and compare d with the crystal structure. Secondary structure transitions and doma in closures defined those parts of the structure which are involved in an induced-fit movement of the enzyme. The presence of more stable hy drogen bonds on the substrate side leads to the assumption that substr ate binding is more specific than cosubstrate binding. Reliable result s were achieved only if water was explicitly included in the simulatio n.