Protein Domain Level Cancer Drug Targets in the Network of MAPK Pathways

Abstract

Proteins in the MAPK pathways considered as potential drug targets for cancer treatment. Considering pathways along with the cross-talks increases their scope to view them as a network of MAPK pathways. Side effect causing targeted domains act as a proxy for drug targets due to its structural similarity and frequent reuse of their variants. We proposed to identify non-repeatable protein domains as the drug targets to disrupt the signal transduction than targeting the whole protein. Network based approach is used to understand the contribution of 52 domains in non-hub, non-essential and intra-pathway cancerous nodes and to identify potential drug target domains. 34 distinct domains in the cancerous proteins are playing vital roles in making cancer as a complex disease and pose challenges to identify potential drug targets. Distribution of domain families follows the power law in the network. Single promiscuous domains are contributing to the formation of hubs like Pkinease, Pkinease Tyr, Ras. Hub nodes are positively correlated with the domain coverage and targeting them would disrupt functional properties of the proteins. EIF 4EBP, alpha Kinase, Sel1, ROKNT and KH 1 are the domains identified as potential domain targets for the disruption of the signaling mechanism involved in cancer.