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XB-IMG-194788

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Figure S2. Prediction of putative TMPRSS2 cleavage sites distal to the γ-inhibitory tract using a molecular docking approach. (A) Schematic diagram illustrating the molecular docking strategy used to predict binding modes of 6-mer peptides corresponding to different segments of the distal region of the γ-inhibitory tract to the catalytic domain of TMPRSS2 which are compatible with proteolysis, i.e. fulfill the selection criteria. (B, C) All binding modes that fulfill the selection criteria for the GAARDF- (B) and GKAADF-peptide (C) are shown. (D) All generated binding modes are shown for the GAAADF-peptide, which lacks positively charged arginine or lysine residues. Peptide backbone carbons and nitrogens (in the same color as the corresponding amino acid residue of the peptide sequence given in the lower left corner) and the side chains of arginine or lysine residues occupying the S1 pocket (with carbons in white and nitrogens in blue) are shown. Bar diagrams demonstrate the percentage of the binding modes which fulfill the selection criteria out of the total number of binding modes (90) generated for each peptide, and indicate the arginine or lysine residue that occupies the S1 pocket. (E) Binding modes for each simulated peptide were subdivided into groups of binding modes that do not fulfill (−) or fulfill (+) the selection criteria. Average values of the root-mean-square deviation (RMSD) were calculated for each individual binding mode k (𝑅𝑀𝑆𝐷௞ തതതതതതതതതത) according to the following equation: 𝑅𝑀𝑆𝐷௞ തതതതതതതതതത = 1 𝑛 − 1෍𝑅𝑀𝑆𝐷௞௝ ௡ ௝ୀଵ where 𝑅𝑀𝑆𝐷௞௝ is the RMSD value calculated between all backbone carbon and nitrogen atoms of a peptide binding mode k and the corresponding atoms of a peptide binding mode j (k≠j) from the same group, n is the total number of peptide binding modes in the corresponding group. ***p<0.001, **p<0.01, Kruskall-Wallis with Dunn’s post hoc test (7≤N≤90).

Image published in: Sure F et al. (2022)

Copyright © 2022. Image reproduced with permission of the Publisher.

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