Figure 7.

Evaluation of the generalized EBMetaD method for butyramide in water. (A) EBMetaD biasing potential is shown as function of Ψ for each of the calculations shown in Fig. 6, i.e., with increasing confidence-band widths (denoted by the scaling factor $\mathit{\epsilon }$). The biasing potential was calculated with Eq. 29, using t_e = 30 ns and t = 320 ns (solid curves), and compared with a calculation using Eq. 27 (dashed lines), in which G(Ψ) = −k_BT ln ρ_MD(Ψ), where ρ_MD(Ψ) is the unbiased probability distribution obtained from an unbiased MD trajectory (Fig. 6). (B) Shown are the values of the reversible work required to enforce the EBMetaD biasing potential for each of the four simulations mentioned above. The work values are derived from the Kullback-Leibler divergence of ρ_MD(Ψ) and ρ_EBMetaD(Ψ) (Fig. 6) using Eq. 30 and compared with calculations based on the biasing potentials in (A) using Eq. 28. The error bars in the work values, based on from a five-block analysis, range from 10⁻³ to 10⁻⁴ kcal/mol.