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Thermodynamics of Aβ 16–21 dissociation from a fibril: Enthalpy, entropy, and volumetric properties
Author(s) -
Rao Jampani Srinivasa,
Mahmoudinobar Farbod,
Su Zhaoqian,
Dias Cristiano L.
Publication year - 2015
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24875
Subject(s) - enthalpy , thermodynamics , chemistry , dissociation (chemistry) , molecular dynamics , potential of mean force , umbrella sampling , entropic force , lennard jones potential , entropy (arrow of time) , internal energy , chemical physics , computational chemistry , physics
Here, we provide insights into the thermodynamic properties of A β 16 − 21dissociation 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 β 16 − 21peptide 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 β 16 − 21. Proteins 2015; 83:1963–1972. © 2015 Wiley Periodicals, Inc.