Protein Folding with the Parallel Replica Exchange Molecular Dynamics Method - Parallel Computing for Bioinformatics and Computational Biology - page 419

Interestingly, AMBER96 / GBSA seems to have this problem fixed. Similar to
OPLSAA / SPC, the number of helical residues, including both the α -helix and the 3 10 -
helix, is typically less than or equal to 3, and only less than 1% of the conformations
exhibit helical content at 310 K. Thus, AMBER96 / GBSA gives quite reasonable
results on the α -helical content as compared to explicit solvent simulation and exper-
iment, and the problem of overestimation of the α -helix seems to have been fixed in
AMBER96.

Temperature Dependence Even though the explicit solvent OPLSAA / SPC
model gives very reasonable results at low temperatures, the temperature depen-
dence is not quite correct. The β -hairpin populations at higher temperatures are way
too high, and the folding transition temperature is also way too high. This is found
to be true with CHARMM and AMBER force fields as well with explicit solvent
models [15]. This should not be very surprising given that most of the modern force
fields are parameterized at room temperature. Nevertheless, we include the temper-
ature dependence data here for all five models to provide information for force field
developers to improve the models.
The β -hairpin populations at various temperatures are calculated with the aver-
age fraction of native contacts and the results are compared with the experimental
populations from the TRP fluorescence yield measurements [38]. Klimov and
Thirumalai [49] have used the average fraction of native contacts to estimate the
β -hairpin population, and here we follow the same approach. Figure 17.12 shows the

T(K)

270 290 310 330 350

0.8

Expt.

0.6

0.70

OPLSAA/SPC
OPLSAA/SGB
AMBER94/GBSA
AMBER96/GBSA
AMBER99/GBSA

0.4

0.2

0.0

0.50

0.30

0.10

270 370 470 570 670

Temperature (K)

Figure 17.12 Comparison of the temperature dependence of the β -hairpin population for
various models. The β -hairpin population is estimated with the average fraction of native
contacts. The experimental results [38] are also shown in the inset for comparison.