Journal Article

FZJ-2017-03062

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Gating Charge Calculations by Computational Electrophysiology Simulations

Machtens, J.-P. (Corresponding author)FZJ* ; Briones, R. ; Alleva, C.FZJ* ; de Groot, B. L. ; Fahlke, C.FZJ*

2017
Cell Press Cambridge, Mass.

This record in other databases:      

Please use a persistent id in citations: doi:10.1016/j.bpj.2017.02.016

Abstract: 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

---

Contributing Institute(s):

1. Zelluläre Biophysik (ICS-4)
2. JARA - HPC (JARA-HPC)

Research Program(s):

1. 552 - Engineering Cell Function (POF3-552) (POF3-552)
2. Mechanisms of Ca2+-activated Cl- channels and lipid scramblases of the TMEM16 family (jics41_20161101) (jics41_20161101)
3. MOLECULAR MODELLING OF BIFUNCTIONAL MEMBRANE TRANSPORT PROTEINS (jics40_20130501) (jics40_20130501)

Appears in the scientific report 2017

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---