Figure 5. Thermodynamics of dihydrofolate reductase.

Dihydrofolate reductase was simulated in boxes of 3 different sizes (A). (B) The distance between C_α atoms of residues 18 and 45 was used as a reaction coordinate. Here, loop M20 is coloured in red. (C) Free energy profiles along the reaction coordinate were constructed from three simulation repeats. Upper panel: 2.5 ns sampling time of which 0.5 ns were discarded for equilibration. Middle panel: 10 ns sampling time of which 2 ns were discarded for equilibration. Bottom panel: 50 ns sampling time of which 10 ns were discarded for equilibration. (D) Autocorrelation times for the interatomic distance between C_α atoms of residues 18 and 45 for simulations in the boxes of different size. The plots in different rows correspond to the interatomic distances used for a harmonic restraint. The shaded areas denote 95% confidence intervals derived from the standard errors over three repeats assuming a normal distribution.