  Mutations in proteins can have deleterious effects on a protein's stability
and function, which ultimately causes particular diseases. Genetically
inherited muscular dystrophies (MDs) include several genetic diseases, which
cause increasing weakness in muscles and disability to perform muscular
functions progressively. Different types of mutations in the gene coding
translates into defunct proteins cause different neuro-muscular diseases.
Defunct protein interactions in human proteome may cause a stress to its
neighboring proteins and its modules. We therefore aimed to understand the
effects of mutated proteins on interacting partners in different muscular
dystrophies utilizing network biology to understand system properties of these
MDs subnetworks .We investigated rigidity and flexibility of protein-protein
interaction subnetworks associated with causative mutated genes showing high
mean interference values in muscular dystrophy. Rigid component related to
EEF1A1 subnetwork and members of 14.3.3 protein family formed the core of
network showed involvement in molecular function related to protein domain
specific binding. CACNA1S and CALM1 showing functionality related to
Voltage-dependent calcium channel demonstrated highest flexibility. The
interconnected subnets of proteins corresponding to known causative genes
having large genetic variants are shared in different muscular dystrophies
inferred towards comorbidity in diseases. The studies demonstrates core network
of MDs as highly rigid, constituting of large intermodular edges and
interconnected hub nodes suggesting high information transfer flow. The core
skeleton of the network is organized in protein specific domain binding. This
suggests neuro-muscular disorders may initiate due to interruption in molecular
function related with the core and its aggression may depend on the tolerance
level of the networks.
