TY  - JOUR
AU  - Machtens, Jan-Philipp
AU  - Briones, Rodolfo
AU  - Alleva, Claudia
AU  - de Groot, Bert L.
AU  - Fahlke, Christoph
TI  - Gating Charge Calculations by Computational Electrophysiology Simulations
JO  - Biophysical journal
VL  - 112
IS  - 7
SN  - 0006-3495
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - FZJ-2017-03062
SP  - 1396 - 1405
PY  - 2017
AB  - Electrical cell signaling requires adjustment of ion channel, receptor, or transporter function in response to changes in membrane potential. For the majority of such membrane proteins, the molecular details of voltage sensing remain insufficiently understood. Here, we present a molecular dynamics simulation-based method to determine the underlying charge movement across the membrane—the gating charge—by measuring electrical capacitor properties of membrane-embedded proteins. We illustrate the approach by calculating the charge transfer upon membrane insertion of the HIV gp41 fusion peptide, and validate the method on two prototypical voltage-dependent proteins, the Kv1.2 K+ channel and the voltage sensor of the Ciona intestinalis voltage-sensitive phosphatase, against experimental data. We then use the gating charge analysis to study how the T1 domain modifies voltage sensing in Kv1.2 channels and to investigate the voltage dependence of the initial binding of two Na+ ions in Na+-coupled glutamate transporters. Our simulation approach quantifies various mechanisms of voltage sensing, enables direct comparison with experiments, and supports mechanistic interpretation of voltage sensitivity by fractional amino acid contributions
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000398956000012
C6  - pmid:28402882
DO  - DOI:10.1016/j.bpj.2017.02.016
UR  - https://juser.fz-juelich.de/record/829347
ER  -