Fig 1.
Stability of Oct4/Sox20bp and Oct4/Sox23bp complexes.
(A) Root mean square deviations (RMSDs) were performed for backbone atoms, with respect to the initial structure, to attain their equilibrium positions and maintain the relaxed state throughout the simulation. (B) Root mean square fluctuation (RMSFs) of protein-backbone residues showing higher fluctuations in the HMG and POUHD domains of Oct4/Sox23bp compared with those of the Oct4/Sox20bp complex. Black represents stability of Oct4/Sox20bp and red represents stability of Oct4/Sox23bp complex.
Fig 2.
Structural arrangements of the Oct4 and Sox2 proteins.
(A) The Oct4/Sox20bp complex with 0 base pairs separating their DNA-binding sites, in which the POUS α1 helix and the HMG α3 helix are involved in protein-protein interactions. (B) Oct4/Sox23bp complex with 3 base pairs separating their DNA-binding sites, in which the POUS α1 helix and the C-terminal loop of the HMG domain are involved in protein-protein interactions. Oct4 is depicted in green, Sox2 in magenta, the DNA surface in grey, and the Oct4 linker region in yellow. Hydrogen bond-interacting residues are also indicated for the complexes.
Table 1.
Residues of the Oct4/Sox20bp and Oct4/Sox23bp complexes involved in bonding and non-bonding interactions.
Fig 3.
Projections of trajectories onto the subspace by the first three eigenvectors.
(A) Projection of trajectories into PC1, PC2, and PC3 for the Oct4/Sox20bp complex. The converged stable conformation and unstable scattered state are shown with red and blue dots, respectively. (B) Projection of trajectories into PC1, PC2, and PC3 for the Oct4/Sox23bp complex. Neither conformational state was stable (scattered blue and red regions). The white dots indicate the intermediate states observed in both complexes.
Fig 4.
Principal modes of motion for the Oct4 and Sox2 proteins.
(A) Dominant motions of Oct4 and Sox2 in the Oct4/Sox20bp complex. (B) Dominant motions of Oct4 and Sox2 in the Oct4/Sox23bp complex. The magnitudes and directions of motion of the residues are indicated by red arrows in the ribbon structure. Oct4 and Sox2 are depicted in green and pink, respectively. The DNA is represented as a stick with heteroatom coloring.
Fig 5.
Dynamic cross-correlation map (DCCM).
(A) DCCM map for the Oct4/Sox20bp complex showing positive and negative correlative motions between the Oct4 and Sox2 domains. (B) DCCM map for Oct4/Sox23bp complex showing positive and negative correlative motions between Oct4 and Sox2 domains. Red represents positive correlations, whereas blue represents negative correlations. The domain regions are labeled.
Fig 6.
Secondary structure changes and residue fluctuations of the Oct4 linker.
(A) Time evaluation of secondary-structure changes, along with RMSD analysis of the Oct4/Sox20bp linker region. (B) Time evaluation of secondary structure changes, along with RMSD analysis of the Oct4/Sox23bp linker region. The secondary structure changes observed for the Oct4/Sox23bp complex are marked in red. (C) RMSFs of linker-region residues 76–92 calculated for 250 ns for both complexes. The residues with relatively high fluctuations for the Oct4/Sox23bp complex are indicated.
Fig 7.
(A) DNA-bend angles for the Oct4/Sox20bp and Oct4/Sox23bp complexes. (B) Helix twist and inclination for the Oct4/Sox20bp and Oct4/Sox23bp complexes. (C) Rises and rolls for the Oct4/Sox20bp and Oct4/Sox23bp complexes. Black represents the Oct4/Sox20bp complex, and red represents the Oct4/Sox23bp complex.
Table 2.
Binding free energy of the Oct4/Sox20bp and Oct4/Sox23bp complexes calculated using the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method.