The energy function includes terms that have been found to be important for protein stability, where the energy of unfolding (∆G) of a target protein is calculated using the equation:
∆G = ∆Gvdw + ∆GsolvH + ∆GsolvP + ∆Ghbond + ∆Gwb + ∆Gel + ∆Smc + ∆Ssc
- ∆Gvdw is the sum of the Van der Waals contributions of all atoms with respect to the same interactions with the solvent.
- ∆GsolvH and ∆GsolvP is the difference in solvation energy for apolar and polar groups, respectively, when going from the unfolded to the folded state.-
- ∆Ghbond is the free energy difference between the formation of an intra-molecular hydrogen-bond compared to inter-molecular hydrogen-bond formation (with solvent).
- ∆Gwb is the extra stabilizing free energy provided by a water molecule making more than one hydrogen-bond to the protein (water bridges) that cannot be taken into account with non-explicit solvent approximations.
- ∆Gel is the electrostatic contribution of charged groups, including the helix dipole.
- ∆Smc is the entropy cost for fixing the backbone in the folded state. This term is dependent on the intrinsic tendency of a particular amino acid to adopt certain dihedral angles.
- ∆Ssc is the entropic cost of fixing a side chain in a particular conformation.
The energy values of ∆Gvdw, ∆GsolvH, ∆GsolvP and ∆Ghbond attributed to each atom type have been derived from a set of experimental data, and ∆Smc and ∆Ssc have been taken from theoretical estimates. The Van der Waals contributions are derived from vapor to water energy transfer, while in the protein we are going from solvent to protein.
For protein-protein interactions, or protein-DNA interactions FoldX calculates ∆∆G of interaction :
∆∆Gab = ∆Gab- (∆Ga + ∆Gb) + ∆Gkon + ∆Ssc
∆Gkon reflects the effect of electrostatic interactions on the kon. ∆Ssc is the loss of translational and rotational entropy upon making the complex.