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Fig 1.

Structure of Ecdysterone.

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Fig 1 Expand

Fig 2.

The binding orientation of AR in complex with A) Testosterone (native ligand) and B) Ecdysterone. The dashed black line represents hydrogen bonding. Pictures were rendered utilizing UCSF Chimera.

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Fig 2 Expand

Fig 3.

The binding orientation of ER

α in complex with A) Estradiol (native ligand) and B) Ecdysterone. The dashed black line represents hydrogen bonding. Pictures were rendered utilizing UCSF Chimera.

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Fig 3 Expand

Fig 4.

The binding orientation of ERβ in complex with A) Estradiol (native ligand) and B) Ecdysterone. The dashed black line represents hydrogen bonding. Pictures were rendered utilizing UCSF Chimera.

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Fig 4 Expand

Fig 5.

A visualization of the electronic properties of Ecdysterone. (A) The optimized structure, (B) molecular electrostatic potential map (isovalue = 0.01e), and (C) HOMO-LUMO representation (isovalue = 0.015e).

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Fig 5 Expand

Fig 6.

RMSD plots of the 250 ns simulated trajectories of A) AR B) ERα and C) ERβ in complex with Ecdysterone and their respective native ligands. (D) RMSD plots of the 250 ns simulated trajectories of Ecdysterone in complex with AR, ER

α ERβ.

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Fig 6 Expand

Fig 7.

RMSF plots of the 250 ns simulated trajectories of A) AR and B) ERα C) ER

β with Ecdysterone and native ligands.

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Fig 8.

Rg plots of the 250 ns simulated trajectories of A) AR and B) ERα and C) ERβ in complex with Ecdysterone and their respective native ligands.

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Fig 8 Expand

Fig 9.

Dynamic occupancy of hydrogen bonding between ligands and various residues of protein in A) ERα-Ecdysterone, B) ERα-Native Ligand, C) AR-Ecdysterone, D) AR-Native Ligand, E) ERβ-Ecdysterone and F) ERβ

-Native Ligand systems.

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Fig 9 Expand

Table 1.

Contributions of various energetic terms to the binding free energy () of the studied protein-ligand complexes, provided as mean ± standard error of the mean. All units are in kcal/mol.

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Table 1 Expand

Fig 10.

A side-by-side representation of the PCA and Free Energy Landscape (FEL) profiles of A) AR - Ecdysterone B) AR - Native Ligand C) ERα - Ecdysterone D) ERα - Native Ligand E) ERβ - Ecdysterone F) ERβ - Native Ligand.

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