Simulation of the thermodynamics of folding and unfolding of the Trp-cage mini-protein TC5b using different combinations of force fields and solvation models

Molecular dynamics simulations based on AMBER force fields (ff96 and ff03) and generalized Born models (igb1 and igb5) have been carried out in order to study folding/unfolding of the Trp-cage mini-protein TC5b. The thermodynamic properties of TC5b were found to be sensitive to the specific version of the solvation model and force field employed. When the ff96/igb5 combination was used, the predicted melting temperature from unfolding simulations was in good agreement with the experimental value of 315 K, but the folding simulation did not converge. The most stable thermodynamic profile in both folding and unfolding simulations was obtained when the ff03/igb5 combination was employed, and the predicted melting temperature was about 345 K, showing over-stabilization of the protein. Simulations using the igb1 version in combination with ff96 or ff03 were difficult to converge within the simulation time limit (50 ns).