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The Dependence of Amyloid‐β Dynamics on Protein Force Fields and Water Models
Author(s) -
Somavarapu Arun Kumar,
Kepp Kasper P.
Publication year - 2015
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201500415
Subject(s) - opls , chemistry , force field (fiction) , molecular dynamics , water model , computational chemistry , crystallography , physics , quantum mechanics
We studied the dynamics of Aβ 40 , involved in Alzheimer's disease, by using 21 methods combined from Amber03, Amber99sb‐ILDN, Charmm27, Charmm22*, OPLS‐2001, OPLS‐2006, OPLS‐2008, Gromos96‐43a1, Gromos96‐53a6, Gromos96‐54a7, and the water models SPC, TIP3P, TIP4P. Major differences in the structural ensembles were systematized: Amber03, Charmm27, and Gromos96‐54a7 stabilize the helices; Gromos96‐43a1 and Gromos53a6 favor the β‐strands (with Charmm22* and Amber99sb‐ILDN in between), and OPLS produces unstructured ensembles. The accuracy of the NMR chemical shifts was in the order: Charmm22*>Amber99sb‐ILDN>OPLS‐2008≈Gromos96‐43a1>Gromos96‐54a7≈OPLS‐2001>OPLS‐2006>Gromos96‐53a6>Charmm27>Amber03. The computed 3 J HNHα ‐coupling constants were sensitive to experiment type and Karplus parameterization. Overall, the ensembles of Charmm22* and Amber99sb‐ILDN provided the best agreement with experimental NMR and circular dichroism data, providing a model for the real Aβ monomer ensemble. Also, the polar water model TIP3P significantly favored helix and compact conformations.