Thermodynamics of Aβ16-21 dissociation from a fibril: Enthalpy, entropy, and volumetric properties

Document Type

Article

Publication Date

11-1-2015

Abstract

Here, we provide insights into the thermodynamic properties of A β16-21 dissociation from an amyloid fibril using all-atom molecular dynamics simulations in explicit water. An umbrella sampling protocol is used to compute potentials of mean force (PMF) as a function of the distance ξ between centers-of-mass of the A β16-21 peptide and the preformed fibril at nine temperatures. Changes in the enthalpy and the entropic energy are determined from the temperature dependence of these PMF(s) and the average volume of the simulation box is computed as a function of ξ. We find that the PMF at 310 K is dominated by enthalpy while the entropic energy does not change significantly during dissociation. The volume of the system decreases during dissociation. Moreover, the magnitude of this volume change also decreases with increasing temperature. By defining dock and lock states using the solvent accessible surface area (SASA), we find that the behavior of the electrostatic energy is different in these two states. It increases (unfavorable) and decreases (favorable) during dissociation in lock and dock states, respectively, while the energy due to Lennard-Jones interactions increases continuously in these states. Our simulations also highlight the importance of hydrophobic interactions in accounting for the stability of A β16-21.

Identifier

84944455435 (Scopus)

Publication Title

Proteins Structure Function and Bioinformatics

External Full Text Location

https://doi.org/10.1002/prot.24875

e-ISSN

10970134

ISSN

08873585

PubMed ID

26264694

First Page

1963

Last Page

1972

Issue

11

Volume

83

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