Protein Folding with the Parallel Replica Exchange Molecular Dynamics Method - Parallel Computing for Bioinformatics and Computational Biology - page 412

about 2.92 kcal / mol (4.75 kT) lower free energy than the native state (as this state is
similar to the intermediate state H from explicit solvent model [15, 41, 44], we also
name it the H state for simplicity in the following). (3) The overall shape of the free
energy contour map, however, is still an “L” shape, which is the same as the con-
tour map for the explicit solvent simulation. This indicates that the folding process is
probably still driven by hydrophobic core collapse [15].
To understand why the SGB continuum solvent model favors nonnative struc-
tures, we analyze the heavily populated state H in detail. Figure 17.8 b shows one
of the representative structures from clustering in state H, and for comparison, we
also show one of the representative structures from the explicit solvent model, which
is basically the native structure (Fig. 17.8 a ). Two interesting observations emerge
from the comparison of these two structures: (1) The hydrophobic residue PHE52
Figure 17.8 Comparison of the lowest free energy structures: ( a ) from the explicit solvent
model, ( b ) from the implicit solvent GB model, and ( c ) from the implicit solvent PB model.
The hydrophobic residues (TRP43, TYR45, PHE52, and VAL54) are represented by spacefill
and charged residues (GLU42, ASP46, ASP47, LYS50, and GLU56) are represented by sticks
with positively charged residues colored dark gray and negatively charged residues colored
light gray, and the rest are represented by ribbons.