## Evaluation of Configurational Entropy Methods from Peptide Folding−Unfolding Simulation

journal contribution

posted on 13.12.2007 by Da-Wei Li, Mina Khanlarzadeh, Jinbu Wang, Shuanghong Huo, Rafael Brüschweiler#### journal contribution

Any type of content formally published in an academic journal, usually following a peer-review process.

A 4-μs molecular dynamics simulation of the second β-hairpin of the B1 domain of streptococcal protein G
is used to characterize the free energy surface and to evaluate different configurational entropy estimators.
From the equilibrium folding−unfolding trajectory, 200 000 conformers are clustered according to their root-mean-square deviation (RMSD). The height of the free energy barrier between pairs of clusters is found to
be significantly correlated with their pairwise RMSD. Relative free energies and relative configurational
entropies of the clusters are determined by explicit evaluation of the partition functions of the different clusters.
These entropies are used to evaluate different entropy estimators for the largest 20 clusters as well as a
subensemble comprising exclusively extended conformers. It is found that the quasi-harmonic entropy estimator
operating in dihedral angle space performs better than the one using Cartesian coordinates. A recent
generalization of the quasi-harmonic approach that computes Shannon entropies of probability distributions
obtained by projecting the conformers along the eigenvectors of the covariance matrix performs similarly
well. For the best entropy estimators, a linear correlation coefficient between 0.92 and 0.97 is found.
Unexpectedly, when correlations between dihedral angles are neglected, the agreement with the reference
entropies improved.