Ethosuximide: subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels

Classical MD simulation of the GIRK2 channel (PDB: 3SYA) in a POPC membrane in presence of the inhibitor Ethosuximide. 

The scope of the study was to find the ETX binding site. We conducted 5 (run1-5 ) runs each 1.5 μs long. The upload contains a .gro, .a tpr, and an .xtc file of each run.  The .xtc files were processed before the upload and contain every 100th frame of the original data.

The corresponding manuscript was uploaded on the bioRxiv (doi: https://doi.org/10.1101/2024.06.04.597296 ).

Simulation paramters:FFs: Amber99sb, Berger lipids, SPC/E water, GAFF2 (ETX), corrected monovalent Lennard–Jones parameters for ionsSoftware: Gromacs 5.1.2.

Time step: 2fsLennard–Jones / electrostatic interactions cut-off: 1.0 nmLong-range electrostatic interactions: Particle-Mesh Ewald algorithm Bonds were constrained with the LINCS algorithmTemperature: 310 K, V-rescale, τ = 0.1 psPressure: 1 bar,  Parirnello-Rahma, τ = 2 ps

Composition of the system:1 GIRK2 channel (PDB: 3SYA), consisting of 4 chains A, B, C, D4 PIP2 bound to the channel, residue name MOL588 POPC Berger lipids, residue name POPC60897 SPC/E water, residue name SOL322 K+,  residue name K274 Cl-, residue name CL10 R-Ethosuximide, residue name ETR10 S-Ethosuximide, residue name ETS