Neurofilaments (NFs) are essential cytoskeletal filaments that impart mechanical 
integrity to nerve cells. They are assembled from three distinct molecular mass 
proteins that bind to each other to form a 10-nm-diameter filamentous rod with 
sidearm extensions. The sidearms are considered to play a critical role in 
modulating interfilament spacing and axonal caliber. However, the precise 
mechanism by which NF protrusions regulate axonal diameter remains to be well 
understood. In particular, the role played by individual NF protrusions in 
specifying interfilament distances is yet to be established. To gain insight 
into the role of individual proteins, we investigated the structural 
organization of NF architecture under different phosphorylation conditions. To 
this end, a physically motivated sequence-based coarse-grain model of NF brush 
has been developed based on the three-dimensional architecture of NFs. The model 
incorporates the charge distribution of sidearms, including charges from the 
phosphorylation sites corresponding to Lys-Ser-Pro repeat motifs. The model also 
incorporates the proper grafting of the real NF sidearms based on the 
stoichiometry of the three subunits. The equilibrium structure of the NF brush 
is then investigated under different phosphorylation conditions. The 
phosphorylation of NF modifies the structural organization of sidearms. Upon 
phosphorylation, a dramatic change involving a transformation from a compact 
conformation to an extended conformation is found in the heavy NF (NF-H) 
protein. However, in spite of extensive phosphorylation sites present in the 
NF-H subunit, the tails of the medium NF subunit are found to be more extended 
than the NF-H sidearms. This supports the notion that medium NF protrusions are 
critical in regulating NF spacings and, hence, axonal caliber.