European Biophysics Journal

, Volume 45, Issue 8, pp 853–859 | Cite as

An in silico study of the effect of SOD1 electrostatic loop dynamics on amyloid‑like filament formation

  • Eamonn F. HealyEmail author
  • Luis Cervantes
Biophysics Letter


Superoxide dismutase [Cu–Zn], or SOD1, is a homo-dimeric protein that functions as an antioxidant by scavenging for superoxides. A wide range of SOD1 variants are linked to inherited, or familial, amyotrophic lateral sclerosis, a progressive and fatal neurodegenerative disease. Aberrant SOD1 oligomerization has been strongly implicated in disease causation, even for sporadic ALS, or SALS, which accounts for ~90 % of ALS cases. Small heat shock proteins (sHSP) have been shown to protect against amyloid fibril formation in vitro, and the sHSP αB-crystallin suppresses in vitro aggregation of SOD1. We are seeking to elucidate the structural features of both SOD1 amyloid formation and αB-crystallin amyloid suppression. Specifically, we have used a flexible docking protocol to refine our model of a SOD1 non-obligate tetramer, postulated to function as a transient desolvating complex. Homology modeling and molecular dynamics (MD) are used to supply the missing structural elements of a previously characterized SOD1 amyloid filament, thereby providing a structural analysis for the observed gain of interaction. This completed filament is then further modified using MD to provide a structural model for protofibril capping of SOD1 filaments by αB-crystallin.


Superoxide dismutase Amyotrophic lateral sclerosis Electrostatic loop αB-crystallin 



The authors wish to acknowledge the support of the National Institute of General Medical Services (1K12GM102745), as well as Welch Foundation (Grant# BH-0018) for its continuing support of the Chemistry Department at St. Edward’s University.

Supplementary material

249_2016_1163_MOESM1_ESM.pdb (353 kb)
Supplementary material 1 (PDB 353 kb)
249_2016_1163_MOESM2_ESM.pdb (694 kb)
Supplementary material 2 (PDB 695 kb)
249_2016_1163_MOESM3_ESM.pdb (458 kb)
Supplementary material 3 (PDB 459 kb)


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Copyright information

© European Biophysical Societies' Association 2016

Authors and Affiliations

  1. 1.Department of ChemistrySt. Edward’s UniversityAustinUSA

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