STRUCTURAL DETERMINANTS OF FLICKERING IN K+ CHANNELS

$1,094P41FY2011RRNIH

Carnegie-Mellon University, Pittsburgh PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our goal is to use classical trajectories of the KcsA channel to elucidate the structural basis of the short-lived nonconductive conformational states of the selectivity filter that are associated with the rapid flickering observed in single-channel recordings. Based on available experimental data, flickering is expected to arise naturally during multi-?s molecular dynamics trajectories of the open E71Q mutant of the KcsA channel. The trajectories will be used to generate new experimentally testable hypotheses regarding the transient conformations of the selectivity filter.

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