Ion Selectivity of α-Hemolysin with β-Cyclodextrin Adapter. II. Multi-Ion Effects Studied with Grand Canonical Monte Carlo/Brownian Dynamics Simulations

• Published in: The journal of physical chemistry. B 2010-03, Vol.114 (8), p.2901-2909
• Main Authors: Egwolf, Bernhard, Luo, Yun, Walters, D. Eric, Roux, Benoît
• Format: Article
• Language: English
• Subjects: Algorithms; B: Biophysical Chemistry; beta-Cyclodextrins - chemistry; Hemolysin Proteins - chemistry; Ions - chemistry; Molecular Dynamics Simulation; Monte Carlo Method
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp906791b

In a previous study of ion selectivity of α-hemolysin (αHL) in complex with β-cyclodextrin (βCD) adapter, we calculated the potential of mean force (PMF) and characterized the self-diffusion coefficients of isolated K+ and Cl− ions using molecular dynamics simulations (Y. Luo et al., “Ion Selectivity of α-Hemolysin with β-Cyclodextrin Adapter: I. Single Ion Potential of Mean Force and Diffusion Coefficient”). In the present effort, these results pertaining to single isolated ions in the wide aqueous pore are extended to take into account multi-ion effects. The grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) algorithm is used to simulate ion currents through the wild-type αHL ion channel, as well as two engineered αHL mutants, with and without the cyclic oligosaccaride βCD lodged in the lumen of the pore. The GCMC/BD current−voltage curves agree well with experimental results and show that βCD increases the anion selectivity of αHL. Comparisons between multi-ion PMFs from GCMC/BD simulations and single-ion PMFs demonstrate that multi-ion effects and pore shape are crucial for explaining this behavior. It is concluded that the narrow βCD adapter increases the anion selectivity of αHL because it reduces the pore radius locally, which decreases the ionic screening and the dielectric shielding of the strong electrostatic field induced by a nearby ring of positively charged αHL side chains.