Tuning ion coordination architectures to enable selective partitioning

¹ Sandia National Laboratories

^* To whom correspondence should be addressed. E-mail: slrempe{at}sandia.gov.

Submitted on February 22, 2007
Revised on March 7, 2007
Accepted on 26 March 2007

	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-Ångström 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.

Key Words: ab initio, ion partitioning, molecular determinents, phase effects, potassium channels, quantum chemistry

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