Mechanism of Ion Recognition by Over-coordination: “The Caress of the Surroundings”[1

Abstract

Transferring Na+ and K+ ions from their preferred coordination states in water to states having different coordination numbers incurs a free energy cost. In several examples in nature, however, these ions readily partition from aqueous-phase coordinations into spatial regions having much higher coordination numbers. In particular, crystallographic data for the celebrated potassium channels show that their binding sites coordinate K+ using eight carbonyl ligands, all within 3.0 A from K+. This makes for twice as many ligands as seen preferentially around K+ in aqueous phase,[2,3] which would seemingly suggest an enormous uphill transition on the free energy surface.We combine quantum, classical, and structural informatics studies to interrogate ion partitioning from low coordinations in water to over-coordinated[4,5] binding sites in proteins. Our results define the important role of the ligand surroundings in driving transitions in ion coordination structure, which underlies ion recognition in some proteins like potassium channels.[6][1]. Jordan, BJ 2007.[2]. Rempe, Asthagiri, and Pratt, PCCP 2004.[3]. Varma and Rempe, Biophys. Chem. 2006.[4]. Varma and Rempe, BJ 2007.[5]. Varma, Sabo, and Rempe, JMB 2008.View Large Image | View Hi-Res Image | Download PowerPoint Slide[6]. Varma and Rempe, JACS 2008.