Fig. 3: Explainable module of TransDSI (PairExplainer) provides partial insights into the protein structural basis of the DSI of USP7-DNMT1. | Nature Communications

Fig. 3: Explainable module of TransDSI (PairExplainer) provides partial insights into the protein structural basis of the DSI of USP7-DNMT1.

From: A protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions

Fig. 3: Explainable module of TransDSI (PairExplainer) provides partial insights into the protein structural basis of the DSI of USP7-DNMT1.The alternative text for this image may have been generated using AI.

a Schematic diagram of PairExplainer working principle: For both DUB and substrate, a sliding window of 3 residues moves along the protein sequence with a step size of 1 residue, performing in silico “knockout” by removing all residues except for the triad within the sliding window. The regions with the lowest change in “Disturbed Score” relative to “TransDSI Score” after knockout are more likely to be the binding sites for DSI (indicated by red arrows). b This heatmap visualizes the effect of each amino acid residue of DNMT1 (from 940 to 1,299) on USP7-DNMT1 interaction, with residues in red exerting positive effects and those in blue no effects. The Lysine residues (K1111, K1113, K1115) of DNMT1 (in the red oval box) harbor relatively higher scores in the importance map, which have been reported to be crucial for the interaction with USP727. c Depiction of USP7-DNMT1 complex (PDB id: 4YOC) modeled in surface representation. Residue importance of the DNMT1 learned from PairExplainer with coloring ranging from low (blue) to high (red) are shown. Inset demonstrates details of USP7-DNMT1 interface, including the acidic pocket of USP7 and KG linker of DNMT1. Source data are provided as a Source Data file.

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