Elizabeth Tuason

Human soluble epoxide hydrolase (sEH) is an enzyme that, when inhibited by the ligand TPPU, has been shown to be an effective treatment against neuropathic pain caused by diabetes in rodents. To find potent sEH inhibitors, different sEH-TPPU conformations (poses) were selected from a previously published study on sEH-TPPU unbinding simulations. For each pose, pharmamacophore-based screens were performed with Pharmit using a set of spatially-organized, features taken from TPPU (e.g. hydrogen bond donors/acceptors, aromatic rings, hydrophobic groups). Ligands that have the same features in the same orientation as the given sEH-TPPU pose were returned as a dataset and were docked onto each of the sEH poses using Schrodinger Glide docking software. Ligands with lowest docking scores for the bound state and not the transition state can be used to initialize new unbinding simulations. furthermore , since ligands with longer residence times (i.e. the amount of time the ligand is bound to its target) have been shown to be more potent treatments, these results can be used to predict which ligands would have the longest residence time or even have alternative bound poses. These ligands could serve as potential drugs for treating pain