Fig 1.
a) Primary and secondary structure of the GR DBD. b) Representation of the crystal structure of the GR DBD/Fkbp5 complex (pdb:3g6p, chain A).
Table 1.
Simulated GR DBD/DNA complexes.
Fig 2.
The absence of the GR DBD dimer partner provokes a strong dynamical alteration on the D-loop.
a) RMSF values of the S1 system, chain A in black and chain B in red, S1A system in purple and S1B system in yellow. The secondary structure of the GR DBD is schematized along the x-axis. b) Principal component analysis of the MD trajectories: projection on the first two eigenvectors in S1, chain A in black and chain B in red, S1A system in purple and S1B system in yellow. c) Average structures of S1, chain A in black and chain B in red, S1A system in purple and S1B system in yellow. d) Time evolution of secondary structure propensities for the S1 system.
Fig 3.
The A477T mutation affects the dimerization interface.
Overall view of the average structures of the S1 (a) and S2 (b) systems showing the location of the dimerization zinc fingers and residues 477.
Table 2.
The A477T mutation alters the GR DBD dimerization interface.
Fig 4.
Thr477 forms hydrogen bond interactions with residues of the dimerization zinc finger that alters its structure.
a) Detailed view of the average structures of the dimerization zinc fingers (chain A) in S1 and S2 systems. b) Time evolution of the distance between the HG1 atom of residue Thr477 (chain A) and the SG atom of Cys492 in the S2 system (chain A). c) Time evolution of the angle between OG1 and HG1 atoms of Thr477 and SG atom of Cys492 in the S2 system (chain A). d) Time evolution of the distance between the H atom of residue 477 and SG atom of Cys492 in S1 and S2 systems (chains A). f) Time evolution of the distance between H atom of Gly478 and SG atom of Cys476 in S1 and S2 systems (chains A).
Fig 5.
The A477T mutation affects polar inter-monomeric interactions.
Average structure of the S1 system showing the main polar interaction between chain A and chain B residues.
Fig 6.
The GRE spacer affects the minor groove width.
Variation of the average minor groove width along the oligomer in S1 (black), S2 (green), S3 (blue) and S4 (magenta) (x = G for S1 and S3 systems, x = A for S2 and S4 systems).
Fig 7.
The GRE spacer sequence alters the propeller and the slide base-pair parameters.
Time evolution of propeller and slide values for S1 (black), S2 (green), S3 (blue) and S4 (magenta) systems. Schematic representations were extracted from Ref. [24].
Fig 8.
Complexes that are more active have lever-arms with a reduced mobility.
a) RMSF values of chain A residues of S1, S2, S3 and S4 systems. b) RMSF values of chain B residues of S1, S2, S3 and S4 systems. The secondary structure of GR DBD is schematized along the x-axis. c) Principal Component Analysis of MD trajectories: projection on the first two eigenvectors of lever arm and D-loop CA atoms in S1, S2, S3 and S4 systems.
Fig 9.
The less active complexes have an altered community structure.
Community structure of the GR DBD (chains A and B) displayed in the three-dimensional structure (a) or in schematic two-dimensional representation (b). The two-dimensional view of the communities depicts the relative size of the communities (number of residues) as colored circles of varying areas and the relative interconnectivity strength as lines of varying thicknesses.