Ligand diffusion in the catalase from Proteus mirabilis: A molecular dynamics study

The role of the channels and cavities present in the catalase from Proteus mirabilis (PMC) was investigated using molecular dynamics (MD) simulations. The reactant and products of the reaction, H2O2 --> 1/2 O-2 + H2O, catalyz ed by the enzyme were allowed to diffuse to and from the active site. Dynam ic fluctuations in the structure are found necessary for the opening of the major channel, identified in the X-ray model, which allows access to the a ctive site. This channel is the only pathway to the active site observed du ring the dynamics, and both the products and reactant use it. H2O and O-2 a re also detected in a cavity defined by the heme and Ser196, which could pl ay an important role during the reaction. Free energy profiles of the ligan ds diffusing through the major channel indicate that the barriers to ligand diffusion are less than 20 kJ mol(-1) for each of the species. It is not c lear from our study that minor channels play a role for access to the prote in active site or to the protein surface.