Figure 3
From: Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease
TcAkt-PH PIP binding site evaluation by NMR and MD simulations. (a) Chemical shift perturbations of TcAkt-PH. The graph includes calculated d-values (see Eq. 4) for each amino acid of TcAkt-PH. (b) Surface display of TcAkt-PH colored by determined d-values according to a gradient. Residues exhibiting high d-values are shown in red (max: 0.69), low d-values in light yellow (min: 0.01), not affected residues below threshold (< 0.008) in white, n.a. residues (due to overlap or missing peaks) are shown in grey. (c) MD derived structure of TcAkt-PH interacting with Ins(1,3,4,5)P4 (a frame was carefully chosen from the last 1 µs MD simulation to showcase the interacting residues adequately): Interacting residues are shown in sticks, contacts in dashed yellow lines, phosphate groups in red (ball representation). (d) H-bonds, ionic interactions, and water bridges plotted as interaction fractions for each interacting residue: Bar charts are normalized over the course of the trajectory. A value of 1 indicates that the respective interaction type persists throughout 100% of the simulation time, while a value greater than 1 signifies multiple instances of the same interaction type between corresponding residue and ligand over the simulation duration (e.g., multiple hydrogen bonds between arginine and the ligand). Additional details on the computed interactions (H-bonds, ionic interactions, and water bridges) can be found in the supplementary information (SI Section 1 ‘Detailed description for computed protein–ligand interactions of TcAkt-PH and Ins(1,3,4,5)P4 shown in Fig. 3d’).
