Figure 3
(a) Direct protein–DNA interactions in the p53 tetramer. (b) 2D projection of the DBD trajectory in the p53 tetramer on the essential subspace along eigenvectors 1 and 2. The conformations in which both the DNA roll and twist parameters for the central TA bases are significantly different from their corresponding values found in standard B-DNA are shown in purple. The essential subspace in which the DNA is distorted is separated along the first eigenvector from the great majority of the p53 tetramer conformations visited during the simulation. (c–e) 3D snapshots of L1 in M1 and M2 (black and red colours, respectively). (c) In the X-ray structure (PDB 3KMD) L1 adopts an outward projection away from the DNA major groove in M1, whereas the same loop tucks into the major groove in M2. (d and e) During the MD simulation, L1 in M1 is observed to move from the outward (d) to an inner conformation (e) with respect to the major groove that is visited for nearly the 40% of the simulation time. In contrast, L1 in M2 maintains the inner conformation of the starting X-ray for nearly 60% of the simulation time (e), but the outward conformation is sampled as well (d).
