Total Energy Calculation through the CG Model.

Our CG model is consistently being upgraded, focusing on the electrostatics of the proteins and their relationship with the solvation of ionizable residues. The total energy of the system is calculated in this model through the following equation:

where ΔGmainCG is the main-chain explicit contribution that includes torsional terms, ΔGelecCG is the electrostatic free energy, ΔGhydroCG is the hydrophobic solvation energy, ΔGpolarCG is the hydrophilic (polar) solvation energy, ΔGvdwCG is the effective van der Waals free energy, and ΔGHBCG is the effective hydrogen bond free energy. Before performing CG energy evaluation we also apply a Monte Carlo proton transfer (MCPT) method to evaluate the ionization states of all of the ionizable residues. In the MCPT approach (37), the MC controls proton transfer between ionizable residues or between one ionizable residue and the bulk. The acceptance probability of the move is determined by standard Metropolis criteria. The actual MCPT can be used for time-dependent study of proton transport processes. However, here we use this approach just to obtained equilibrated ionization states. After the MCPT procedure the CG energies are evaluated by the total energy equation.