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Single-cut predictor (FoldX version)
Standard molecular mechanics force fields do not explicitly account for the backbone and
side chain entropy, which is not needed to calculate dynamics. For our purposes entropy
is important, since it is possible that changes in freedom of motion influence
conformational change. Stability is in fact measured in terms of free energy of folding
rather than enthalpy[1]. Therefore we sought to improve the method by using the FoldX
force field[122]. The fundamental difference between the FoldX and OPLS-All Atom
force fields is that the former is an Empirical Effective Energy Function, based entirely
on experimental data. FoldX includes terms that estimate the entropic cost of
constraining the backbone and side chains in particular conformations. The interaction
with solvent is treated mostly implicitly, although persistent entrained water molecules
are treated explicitly. Other terms account for Van der Waals, hydrogen bonding,
electrostatic, and steric interactions.
In the FoldX version of the single-cut predictor, the energy minimization step described
above (for the TINKER version) was still carried out using the OPLS-All Atom force
field, but in the energy evaluation step, also described above, calculation of the fragment
energy was now carried out using the FoldX force field. All other steps were carried out
exactly as for the TINKER version.
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