The alanine dipeptide was built with YASARA,21 adding acetyl‐ and N‐methyl capping groups. The system consisted of ∼3000 atoms (32 peptide atoms, 981 water molecules, and three ion pairs, that is, 0.98% NaCl). The force field was AMBER03, simulations were run at 298 K with the protocols described in the caption of Figure 6. After an equilibration period of 1 ns, the current φ/ψ dihedrals were calculated every 50 fs and mapped to a two‐dimensional grid with a resolution of 5° (72 × 72 bins), then the corresponding counter was incremented. After a microsecond, the probability in each grid bin was obtained by dividing with the total number of counts, converted to a free energy using the well known Boltzmann formula Energy = −BoltzmannConstant × 298 × ln(Probability), shifted so that the energy minimum was at 0, and visualized using the marching squares algorithm for seven contour levels with a spacing of 4 kJ/mol. The YASARA macro used to perform these tasks can be found in the documentation of the free YASARA View program version 15 or later, at Commands > Options > Tables > Tabulate.
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