Water movement during ligand unbinding from receptor site.

An 1-ns unbinding trajectory of retinol from the bovine serum retinol-binding protein has been obtained from molecular dynamics simulations. The behavior of water during ligand unbinding has never been studied in detail. I described a new method for defining a binding site, located the water molecules involved in the binding site, and examined their movements during unbinding. I found that there were only small changes in the binding site. During unbinding, the number of water molecules inside the binding site decreased, with some water molecules exhibiting movements similar in magnitude to bulk water, and there were rearrangements of the hydrogen bonds. This work represents the first detailed study of the behavior of water during an unbinding process.