Analysis methods for identifying coordinated movements during ligand unbinding

Molecular dynamics simulations have been applied to unbind biological ligands from their receptors. Conformation changes are observed in the biomolecules during unbinding, but there exists no systematic method to detect these conformation changes. In this work, we have used 'essential dynamics' (ED) and projection to latent structures (PLS) to investigate the conformation changes of the bovine serum retinol-binding protein when retinol unbinds from its receptor site. The results of these analyses characterise a large proportion of the movements that occur during unbinding. We find that the loop regions of retinol-binding protein exhibit the largest movements during unbinding. The sudden changes in unbinding speed during the unbinding process appear not to be caused by sudden changes in protein structure.