title: Multiscale Simulations of a Two-Pore Potassium Channel.
abstract: Two-pore domain channels control cell excitability by modulating background potassium currents in response to several physicochemical stimuli. Thanks to the many crystal structures available, the TRAAK channel is one of the most studied, but little is known about its functional dynamics. Here, we explore TRAAK functionality complementing molecular dynamics with Brownian dynamics in a multiscale-modeling framework. We identify potential states of the channel that can prevent ion conduction, and we demonstrate that the suppression of currents is consistent with the presence of lipids inside the cavity.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - Università di Bologna , via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Masetti
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush University Medical Center , Chicago 60612, Illinois, United States.
authors.forename: Claudio
authors.initials: C
authors.lastname: Berti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - Università di Bologna , via Belmeloro 6, 40126 Bologna, Italy.|CompuNet, Istituto Italiano di Tecnologia , via Morego 30, 16163 Genova, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ocello
authors.affiliation: CompuNet, Istituto Italiano di Tecnologia , via Morego 30, 16163 Genova, Italy.
authors.forename: Giovanni Paolo
authors.initials: GP
authors.lastname: Di Martino
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - Università di Bologna , via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.affiliation: DEI, ARCES, University of Bologna and IUNET , via Venezia 260, 47521 Cesena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiegna
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - Università di Bologna , via Belmeloro 6, 40126 Bologna, Italy.|CompuNet, Istituto Italiano di Tecnologia , via Morego 30, 16163 Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
mesh_terms: D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D007477:Ions; D015221:Potassium Channels; D011188:Potassium