title: Diffusion constant of K+ inside Gramicidin A: a comparative study of four computational methods.
abstract: The local diffusion constant of K(+) inside the Gramicidin A (GA) channel has been calculated using four computational methods based on molecular dynamics (MD) simulations, specifically: Mean Square Displacement (MSD), Velocity Autocorrelation Function (VACF), Second Fluctuation Dissipation Theorem (SFDT) and analysis of the Generalized Langevin Equation for a Harmonic Oscillator (GLE-HO). All methods were first tested and compared for K(+) in bulk water--all predicted the correct diffusion constant. Inside GA, MSD and VACF methods were found to be unreliable because they are biased by the systematic force exerted by the membrane-channel system on the ion. SFDT and GLE-HO techniques properly unbias the influence of the systematic force on the diffusion properties and predicted a similar diffusion constant of K(+) inside GA, namely, ca. 10 times smaller than in the bulk. It was found that both SFDT and GLE-HO methods require extensive MD sampling on the order of tens of nanoseconds to predict a reliable diffusion constant of K(+) inside GA.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Artem B
authors.initials: AB
authors.lastname: Mamonov
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kurnikova
authors.forename: Rob D
authors.initials: RD
authors.lastname: Coalson
mesh_terms: D002414:Cations, Monovalent / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D004058:Diffusion; D006096:Gramicidin / Q000737:chemistry; D007473:Ion Channels / Q000737:chemistry*; D008432:Mathematical Computing; D011188:Potassium / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D002414:Cations, Monovalent; D007473:Ion Channels; D014867:Water; D006096:Gramicidin; D011188:Potassium