title: Tuning ion coordination architectures to enable selective partitioning.
abstract: K+ ions seemingly permeate K-channels rapidly because channel binding sites mimic coordination of K+ ions in water. Highly selective ion discrimination should occur when binding sites form rigid cavities that match K+, but not the smaller Na+, ion size or when binding sites are composed of specific chemical groups. Although conceptually attractive, these views cannot account for critical observations: 1), K+ hydration structures differ markedly from channel binding sites; 2), channel thermal fluctuations can obscure sub-Angström differences in ion sizes; and 3), chemically identical binding sites can exhibit diverse ion selectivities. Our quantum mechanical studies lead to a novel paradigm that reconciles these observations. We find that K-channels utilize a "phase-activated" mechanism where the local environment around the binding sites is tuned to sustain high coordination numbers (>6) around K+ ions, which otherwise are rarely observed in liquid water. When combined with the field strength of carbonyl ligands, such high coordinations create the electrical scenario necessary for rapid and selective K+ partitioning. Specific perturbations to the local binding site environment with respect to strongly selective K-channels result in altered K+/Na+ selectivities.
authors.affiliation: Computational Bioscience Department, Sandia National Laboratories, Albuquerque, New Mexico 87185, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Varma
authors.forename: Susan B
authors.initials: SB
authors.lastname: Rempe
mesh_terms: D001665:Binding Sites; D002414:Cations, Monovalent; D015640:Ion Channel Gating; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D011789:Quantum Theory; D012964:Sodium / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D002414:Cations, Monovalent; D015221:Potassium Channels; D014867:Water; D012964:Sodium; D011188:Potassium