title: Cation-pi interactions: an energy decomposition analysis and its implication in delta-opioid receptor-ligand binding.
abstract: The nature and strength of the cation-pi interaction in protein-ligand binding are modeled by considering a series of nonbonded complexes involving N-substituted piperidines and substituted monocylic aromatics that mimic the delta-opioid receptor-ligand binding. High-level ab initio quantum mechanical calculations confirm the importance of such cation-pi interactions, whose intermolecular interaction energy ranges from -6 to -12 kcal/mol. A better understanding of the electrostatics, polarization, and other intermolecular interactions is obtained by appropriately decomposing the total interaction energy into their individual components. The energy decomposition analysis is also useful for parametrizing existing molecular mechanics force fields that could then account for energetic contributions arising out of cation-pi interactions in biomolecules. The present results further provide a framework for interpreting experimental results from point mutation reported for the delta-opioid receptor.
authors.affiliation: Department of Chemistry, Department of Medicinal Chemistry, and Minnesota Supercomputer Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA. ymo@xencor.com
authors.forename: Yirong
authors.initials: Y
authors.lastname: Mo
authors.forename: Govindan
authors.initials: G
authors.lastname: Subramanian
authors.forename: Jiali
authors.initials: J
authors.lastname: Gao
authors.forename: David M
authors.initials: DM
authors.lastname: Ferguson
mesh_terms: D002412:Cations / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D002412:Cations; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D010880:Piperidines; D017465:Receptors, Opioid, delta