  The unbinding process of a protein-ligand complex of major biological
interest was investigated by means of a computational approach at atomistic
classical mechanical level. An energy minimisation-based technique was used to
determine the dissociation paths of the system by probing only a relevant set
of generalized coordinates. The complex problem was reduced to a
low-dimensional scanning along a selected distance between the protein and the
ligand. Orientational coordinates of the escaping fragment (the ligand) were
also assessed in order to further characterise the unbinding. Solvent effects
were accounted for by means of the Poisson--Boltzmann continuum model. The
corresponding dissociation time was derived from the calculated barrier height,
in compliance with the experimentally reported Arrhenius-like behaviour. The
computed results are in good agreement with the available experimental data.
