Conduction and Gating Properties of the TRAAK Channel from Molecular Dynamics Simulations with Different Force Fields

Figures

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  Figure 1. (a) Representative snapshot of the simulation system where the protein is shown in cartoon representation, and the lipid molecules and the potassium ions are represented with van der Waals spheres. The two subunits of the channel are displayed in white and gray colors. Water molecules and bulk ions are omitted for the sake of clarity. (b) Close-up view of the SF in the two initial configurations considered in this study (only three out of the four chains are shown). The residue name of the amino acids that contribute to the SF from the two P-loop regions of each subunit (P1 and P2) are also shown. Ion binding sites are labeled S0 to S4.

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  Figure 2. Comparison of the root-mean-square deviation (RMSD) of the SF backbone atoms evaluated in the four sets of simulations. Blue, green, orange, and red correspond to the AMBER-KK, AMBER-KWK, CHARMM-KK, and CHARMM-KWK sets, respectively.

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  Figure 3. Sketch-map representation of the conformational space sampled by the SF during all of the simulations considered in this study. The recurrent conformational states observed are labeled from I (native/conductive state) to VII. Representative configurations of each conformational state are shown and mapped onto the low-d space with solid colored circles. Blue, green, orange, and red correspond to the AMBER-KK, AMBER-KWK, CHARMM-KK, and CHARMM-KWK sets, respectively. The size of the points is proportional to the populations of the main states using a logarithmic scale. Chains A and B are colored in white and gray, respectively. Flipped carbonyls are highlighted in yellow.

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  Figure 4. (a) Representative configuration of the up and down states of the protein at one of the interfaces between the two subunits of the channel. The fenestration that appears in the down state at the TM2-TM4 interface. (b) Scatter plots of the distance between the TM2 and TM4 helices of different subunits obtained from the AMBER and CHARMM sets of simulations are highlighted. Blue and orange circles correspond to the maxima of the AMBER and CHARMM distributions, respectively. A and B refer to the two subunits of the channel.

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  Figure 5. (a) Presence of lipid atoms in the cavity of the TRAAK channel in the AMBER and CHARMM sets of simulations. (b) POPC molecule in stick representation highlighting in yellow the atoms used in the analysis presented in (a) with their corresponding labels.

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  Figure 6. Comparison between typical configurations of lipids facing the internal cavity of the channel obtained with the (a) AMBER and (b) CHARMM force fields. The orientation of the protein is identical in both snapshots. Lipids are depicted in van der Waals representation in blue and orange, respectively. The protein is depicted in gray and the up state is shown in (a), while the down state is displayed in (b).