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Development of DHODH inhibitors incorporating virtual screening, pharmacophore modeling, fragment-based optimization methods, ADMET, molecular docking, molecular dynamics, PCA analysis, and free energy landscape

Fig 5

Molecular dynamics analysis of compounds 65(blue) and 66(black) and DUH(red) with DHODH.

(A) The RMSD of compounds 65 and 66、DUH with DHODH. Compound 65 is shown as blue lines, compound 66 is in the black line. DUH is in the red line. (B) The RMSF of compounds 65 and 66 and DUH with DHODH. Compound 65 is shown as blue lines, compound 66 is in the black line. DUH is in the red line. (C) The Rg of compounds 65 and 66 and DUH with DHODH. Compound 65 is shown as blue lines, compound 66 is in the black line. DUH is in the red line. (D) The Area of compounds 65 and 66 and DUH with DHODH. Compound 65 is shown as blue lines, compound 66 is in the black line. DUH is in the red line. (E) The Hydrogen bond number of compound 65 with DHODH. (F) The Hydrogen bond number of compound 66 with DHODH. (G) The Hydrogen bond number of compound DUH with DHODH. (H) The total energy of compounds 65 and 66 and DUH with DHODH. Compound 65 is shown as blue lines, compound 66 is in the black line. DUH is in the red line.

Fig 5

doi: https://doi.org/10.1371/journal.pone.0342461.g005