Yapısal bilgiyi kullanarak insan protein-protein etkileşim ağının ve kanser proteinlerinin analizi

Protein-protein interaction networks reveal that some proteins are highly connectedto others (acting as hub proteins), whereas some others have a few interactions. Thesame or overlapping binding sites should be repeatedly used in hub proteins (singleinterface hub proteins) making them promiscuous. Alternatively, multi-interface hubproteins make use of several distinct binding sites to bind to different partners.Understanding the interactions with respect to their physical and chemical propertiesrequires the atomistic details of the proteins, namely the three-dimensional structures.Then again, cancer-related proteins are more likely to act as hubs in interactionnetworks. In this thesis, we investigate ?what features of cancer-related proteininterfaces make them act as hubs? and ?how it is possible for them to bind to manydifferent proteins with varying affinity?. We provide a detailed analysis of humanprotein-protein interaction network including cancer-related interactions. First weanalyze the global behavior of cancer-related proteins, second we hold a structuralperspective to elucidate how these proteins interact and figure out which interactionscan occur simultaneously and which ones exclude each other. The results reveal thatcancer-related proteins tend to interact with their partners through distinct interfaces,thus corresponding mostly to multi-interface hubs (56% of cancer-related proteins aremulti-interface) and constituting the nodes with higher essentiality in the network (76%of them are essential). In addition, they have smaller, more planar, more charged andless hydrophobic binding sites compared to non-cancer ones which may indicate lowaffinity and high specificity of the cancer-related interactions. These findings might beimportant in obtaining new targets in cancer as well as finding the details of specificbinding regions of putative drug candidates in cancer.