ACID-UNFOLDING OF APOMYOGLOBIN

Calculating the folding free energy

In general, first principals theoretical calculations of the folding free energy using all-atom models for proteins and solvent are extremely hard. The major difficulty here lies in the need to sample the enormous conformational space of protein/solvent system. Another problem usually arises from the uncertainty about the structure of the unfolded state, but here the unfolding trajectory provides a reasonable ensemble of structural models. To avoid the first difficulty, we use the Poisson-Boltzmann/Surface Area approach in which solvent is represented implicitly as continuum with the dielectric properties of water, and the protein structure variability is represented by the ensemble of snapshots. The hydrophobic effect is taken into account a by the surface-energy term proportional to the solvent-accessible area of the protein. The protein's change in conformational entropy in going from the folded to the completely unfolded state is estimated using per-residue parameters proposed by D'Aquino and Doig and Sternberg.

E-mail: onufriev@cs.vt.edu