Molecular mechanics and molecular dynamics study on azurin using extensible and systematic force field (ESFF)

A systematic study on the assessment of predictive power of extensible and systematic force field (ESFF) has been carried out by taking azurin as a model metalloprotein. Both molecular mechanics (MM) and molecular dynamics (MD) calculations have been performed on native azurin. In addition, the effects of metal ion substitution and mutation of axial methionine have been investigated. MM calculations with axial ligand restraints reasonably predict the structures of native and engineered azurins. It is also evident from the MD simulations that the average structures are similar to that of corresponding X-ray structures. The overall conformation of the engineered and mutated azurins is also akin to that of native protein. However, significant changes are observed in metal ion binding site upon substitution and axial mutation. It is found that the calculated change in strain energy linearly varies with the corresponding experimental redox potentials of engineered azurins.