Chemistry

Evaluation of configurational entropy methods from peptide folding-unfolding simulation

Document Type

Article

Abstract

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. © 2007 American Chemical Society.

Publication Title

Journal of Physical Chemistry B

Publication Date

12-13-2007

Volume

111

Issue

49

First Page

13807

Last Page

13813

ISSN

1520-6106

DOI

10.1021/jp075220e

Keywords

computer simulation, free energy, function evaluation, peptides

Cross Post Location

Student Publications

Link to Full Text

Share

COinS