Rigidity and flexibility in protein-protein interaction networks: a case study on neuromuscular disorders

Background Mutations in proteins can have deleterious effects on a protein’s stability and function, which ultimately causes particular diseases. Genetically inherited muscular dystrophies include several genetic diseases, which cause increasing weakness in muscles and disability to perform muscular functions progressively. Different neuro-muscular diseases are caused by different types of mutations in the gene coding. Mutations in genes make defunct proteins or none at all. Defunct or missing protein interactions in human proteome may cause a stress to its neighboring proteins and subsequently to modules it is involved in. Network biology is utilized to gain knowledgeable insights on system properties of complex protein-protein interaction maps governing affected cellular machinery due to disease causing mutations. We therefore aimed to understand the effects of mutated proteins on interacting partners in different muscular dystrophies. Results 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 Eukaryotic Translation Elongation Factor 1 Alpha 1 (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. Core nodes of core modules showed high modular overlapping and bridgeness values. The subnetworks showing highest flexibility comprised of seed nodes Calcium channel, voltage-dependent, L type, alpha 1S subunit (CACNA1S) and calmodulin 1 (CALM1) showing functionality related to Voltage-dependent calcium channel. The interconnected subnet of proteins corresponding to known causative genes having large genetic variants are shared in different Muscular dystrophies (MDs) inferred towards comorbidity in diseases. Conclusion The studies demonstrates core network of MDs as highly rigid component constituting of large intermodular edges and interconnected hub nodes suggesting high information transfer flow.The core skeleton of the network are organized in protein binding and 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.