ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations
Fig 1
Heat capacity curves of ApoE isoforms.
(A) The heat capacity (Cv) curves computed using WHAM on REX/DMD trajectories for ApoE2 (black), ApoE3 (red) and ApoE4 (blue) in the range of 275 to 400 K show intermediates states that appear at different temperatures for each isoform. The position of the first peak (i.e., unfolding of the hydrophobic core of the protein) suggests that ApoE4 is less thermally stable than ApoE2 and ApoE3. (B-D) Cv curves of individual ApoE isoforms including the error bars (shaded grey area). The shaded grey area in panels B-D represents the statistical uncertainty (i.e., the square root of the variance of the specific heat) in the WHAM estimation of heat capacity. Local minima in the curves at temperatures T1, T2, T3, and T4 represent different conformational states of the protein for each ApoE variant.