ASM 2019

Poster (P43)


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.

References

  1. B. Bagchi, Water in Biological and Chemical Processes: From Structure and Dynamics to Function, Cambridge University Press: Cambridge, U.K., 2013.
  2. W-T. Chen, C-J. Hong, Y-T. Lin, W-H. Chang, H-T. Huang, J-Y. Liao, Y-J. Chang, Y-F. Hsieh, C-Y. Cheng, H-C. Liu, Y-R. Chen, I-H. Cheng, Amyloid-beta (Aβ) D7H mutation increases oligomeric Aβ42 and alters properties of Aβ-Zinc/Copper assemblies, PLoS One 7 (2012) e35807.
  3. K. Ono, M. M. Condron, D. B. Teplow, Effects of the English (H6R) and Tottori (D7N) familial Alzheimer disease mutations on amyloid β-protein assembly and toxicity, J. Biol. Chem. 285 (2010) 23186-23197.
  4. I. Benilova, R. Gallardo, A. A. Ungureanu, V. C. Cano, A. Snellinx, M. Ramakers, C. Bartic, F. Rousseau, J. Schymkowitz, B. D. Strooper, The Alzheimer disease protective mutation Ala2Thr modulates kinetic and thermodynamic properties of Aβ aggregation, J. Biol. Chem. 289 (2014) 30977-30989.

 

Abstract List Program