Parent dataset and code from: Atomistic Mechanisms of the regulation of small conductance Ca 2+ -activated K + channel (SK2) by PIP2

Small conductance Ca 2+ -activated K + channels (SK, K Ca 2) are gated solely by intracellular microdomain Ca 2+. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca 2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in concert with Ca 2+ -CaM in the SK channel activation. Our computational study affords evidence for the critical role of the amino acid residue R395 in the S6 transmembrane domain, which is localized in propinquity to the intracellular hydrophobic gate. This ..., See the PNAS publication for a full description and references
Computational modeling of hSK2 channel to generate starting structures for MD simulations:
The generation of structural models for the hSK2 channel was achieved via three stages using Rosetta molecular modeling (Online Supplemental Fig. S1) as described below.
Electron density map refinement:
In the first stage, we refined and converted three states of the hSK4-CaM cryo-EM structures (PDB IDs: 6CNM, 6CNN, and 6CNO) into Rosetta-optimized energy with Rosetta 2021 software. Cryo-EM refinement was performed with side chains only being optimized. This conversion facilitated the energy terms of these structures to align with Rosetta's scoring function (Score.gd2), leading to improved homology modeling. We used a modified version of the Rosetta demo included in the Rosetta software(https://new.rosettacommons.org/demos/latest/public/electron_density_structure_refinement/structure_refinement) (7, 8).
Homology modeling of hSK..., , # Parent dataset and code from: Atomistic Mechanisms of the regulation of small conductance Ca 2+ -activated K + channel (SK2) by PIP2

[https://doi.org/10.5061/dryad.ksn02v7dj](https://doi.org/10.5061/dryad.ksn02v7dj)

## Description of the data and file structure

README file for parent dataset linked to 5 dataset child submissions for the article titled:

Atomistic mechanisms of the regulation of small conductance Ca 2+ -activated K + channel (SK2) by PIP2

File author Dr. Ryan Woltz. For questions please email [[e-mail]](mailto:[e-mail]).

Document written 2024/08/12

Requirements to load and visualize trajectories.

-vmd\
-minimum 96GB of RAM. (if you do not have this load with the \"skip\" or \"step\" in vmd)\
-UCSF Chimera\
-hole2\
TTClust

IMPORTANT NOTES:

1. This deposit does not include scripts to run programs TTClust, hole2, or UCSF chimera To replicate all figures in the PNAS paper please download these programs. methods for these programs are found in the...