Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: Mechanical probes of SOD1 predict systematic trends in metal and dimer
  affinity of ALS-associated mutants   Mutations and oxidative modification in the protein Cu,Zn superoxide
dismutase (SOD1) have been implicated in the death of motor neurons in
amyotrophic lateral sclerosis (ALS), a presently incurable, invariably fatal
neurodegenerative disease. Here we employ steered, all-atom molecular dynamics
simulations in implicit solvent to investigate the significance of either
mutations or post-translational modifications (PTMs) to SOD1 on metal affinity,
dimer stability, and mechanical malleability. The work required to induce
moderate structural deformations as a function of sequence index constitutes a
"mechanical fingerprint" measuring structural rigidity in the native basin,
from which we are able to unambiguously distinguish wild-type (WT) SOD1 from
PTM variants, and measure the severity of a given PTM on structural integrity.
The cumulative distribution of work values provided a way to cleanly
discriminate between SOD1 variants. Disulfide reduction destabilizes dimer
stability more than the removal of either metal, but not moreso than the
removal of both metals. Intriguingly, we found that disulfide reduction
mechanically stabilizes apo SOD1 monomer, underscoring the differences between
native basin mechanical properties and equilibrium thermodynamic stabilities,
and elucidating the presence of internal stress in the apo state. All PTMs and
ALS-associated mutants studied showed an increased tendency to lose either Cu
or Zn, and to monomerize- processes known to be critical in the progression of
ALS. The valence of Cu strongly modulates its binding free energy. As well,
several mutants were more susceptible to loss of metals and monomerization than
the disulfide-reduced or apo forms of SOD1. Distance constraints are required
to calculate free energies for metal binding and dimer separation, which are
validated using thermodynamic cycles.

26
The categories of this paper are: bayes-an
25
The categories of this paper are: patt-sol
0
The categories of this paper are: hep-ph
18
The categories of this paper are: econ
3
The categories of this paper are: physics
30
The categories of this paper are: q-alg
1
The categories of this paper are: cs
24
The categories of this paper are: dg-ga
5
The categories of this paper are: gr-qc
17
The categories of this paper are: q-fin
37
The categories of this paper are: supr-con
9
The categories of this paper are: nlin
14
The categories of this paper are: math-ph
21
The categories of this paper are: adap-org
6
The categories of this paper are: astro-ph
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The categories of this paper are: eess