Extended Data Fig. 2: Structural analysis of capivasertib (bound ligand in 4GV1) and five de novo generated molecules (Mol. ID 1–5) that were selected for experimental validation. | Nature Machine Intelligence

Extended Data Fig. 2: Structural analysis of capivasertib (bound ligand in 4GV1) and five de novo generated molecules (Mol. ID 1–5) that were selected for experimental validation.

From: Target-specific de novo design of drug candidate molecules with graph-transformer-based generative adversarial networks

Extended Data Fig. 2

(a) Initial binding orientations of capivasertib, Molecules 1 and 2 at the starting point of molecular dynamics (MD) simulations. (b) Key protein-ligand interactions observed during MD simulations, visualised with interacting residues and interaction types. The depicted poses represent the most populated conformations from each simulation. (c) Root-mean-square deviation (RMSD) values of capivasertib, Molecules 1 and 2 in complex with AKT1. (d) Root-mean-square fluctuation (RMSF) values of ligand atoms in the same complexes. Abbreviations: I-VII represent β-sheet numbers, g.l represents glycine-rich loop, c.l represents catalytic loop, GK represents gatekeeper residue, and xDFG represents highly conserved kinase residues; linker represents the loop that connects the hinge domain to αChelix. Gray dashed lines represent Van der Waals interactions. Blue lines represent hydrogen bonds and water bridges. Green lines indicate halogen bonds. Yellow dashed lines represent salt bridges. Directional interactions were noted only when the occupancy value exceeded 10%; however, for visual clarity, occupancy values of the water bridges were stated only when they exceeded 30%.

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