title: Ion conductance vs. pore gating and selectivity in KcsA channel: modeling achievements and perspectives.
abstract: KcsA potassium channel belongs to a wide family of allosteric proteins that switch between closed and open states conformations in response to a stimulus, and act as a regulator of cation activity in living cells. The gating mechanism and cation selectivity of such channels have been extensively studied in the literature, with a revival emphasis these latter years, due to the publication of the crystallized structure of KcsA. Despite the increasing number of research and review papers on these topics, quantitative interpretation of these processes at the atomic scale is far from achieved. On the basis of available experimental and theoretical data, and by including our recent results, we review the progresses in this field of activity and discuss the weaknesses that should be corrected. In this spirit, we partition the channel into the filter, cavity, extra and intracellular media, in order to analyze separately the specificity of each region. Special emphasis is brought to the study of an open state for the channel and to the different properties generated by the opening. The influence of water as a structural and dynamical component of the channel properties in closed and open states, as well as in the sequential motions of the cations, is analyzed using molecular dynamics simulations and ab initio calculations. The polarization and charge transfer effects on the ions' dynamics and kinetics are discussed in terms of partial charge models.
authors.affiliation: Laboratoire de Physique Moléculaire UMR CNRS 6624, Université de Franche-Comté, La Bouloie, 25030, Besançon Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Boiteux
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kraszewski
authors.forename: Christophe
authors.initials: C
authors.lastname: Ramseyer
authors.forename: Claude
authors.initials: C
authors.lastname: Girardet
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D004058:Diffusion; D004553:Electric Conductivity; D015640:Ion Channel Gating; D007700:Kinetics; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry
chemical_list: D015221:Potassium Channels; D014867:Water; D011188:Potassium