Neurochemical receptors are important targets for drug design. Two important aspects of ligand binding in these receptors include the attraction of the ligand to the active-site and the effect of displacing the waters of solvation. The affect of solvtaion is more thoroughly understood in hydrophilic active sites than in hydrophobic active sites. In order to investigate the affect of solvation on hydrophobic active-sites, we have studied ligand binding and water displacement in two hydrophobic active sites, the acetylcholine binding protein and the � opioid receptor. We used crystal structures of these two proteins to obtain a model of each active-site. Morphine, cocaine, and met-enkephalin were docked in the active-sites, and these ligand protein complexes were then optimized using M062X/6-31g. Interaction energies between the ligands and the proteins were calculated using M062X and MP2 with the 6-311+G* basis set. The role of water was explored by placing explicit waters of solvation both in the empty active-sites and around the ligands. The energy required to displace the waters upon ligand binding was calculated using the same methods mentioned above. Preliminary results suggest that solvation plays a larger role than ligand-active-site attraction.

Role of solvation in the binding of morphine, met-enkephalin, and other ligands to the acetylcholine binding protein and � opioid receptor

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.