Effect of Mutations on Hydration Environment of Amyloid-β
Leena Aggarwal and Parbati Biswas*
Department of Chemistry, University of Delhi, Delhi-110007
*pbiswas[at]chemistry.du.ac.in
An analysis of the structure and dynamics of hydration water [1] obtained from the atomistic MD simulations of the wild type full length Aβ42, its familial Alzheimer`s disease mutants, i.e, Taiwan (D7H) [2], Tottori (D7N) and English (H6R) [3] and the protective A2T [4] mutant in explicit water is presented. The extent to which these mutations located at Aβ N-terminus modify the structural order and dynamics of water molecules around Aβ is examined through radial distribution function, tetrahedral order parameter and water residence times. The water molecules are found to be less ordered around Taiwan, Tottori and English mutants while more ordered around the protective A2T mutant as compared to those around wild type Aβ. The residence times of water molecules in the first hydration shell of the wild type Aβ42 are higher than those of Taiwan, Tottori and English mutants while lower than that of the A2T mutant. Our findings indicate that the effect of specific mutations on the hydration structure and dynamics of wild type Aβ may be correlated with the changes in the charge and hydrophobicity of the protein.
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