Hydration plays a key role in the structural stability and functions of proteins. In soluble proteins some of the backbone hydrogen bonds are not surrounded by enough non-polar groups to prevent water interactions, thus affecting the local stability of the hydrogen bonds. These hydrogen bonds, referred to as under-dehydrated hydrogen bonds or dehydrons, seek shielding from water molecules by associating with other partners such as ligands or proteins, thus making them adhesive. This property has been used to identify regions in proteins that are likely to engage in protein – protein interactions (PPI)1. Here, we have extended this concept to query a dataset of 50 aggregating proteins, to systematically investigate sites that may nucleate. Aggregation can be thought of as form of PPI resulting from misfolding or mutation that usually leads to loss of normal functions and, has been associated with a wide range of diseases. Therefore, identification of aggregation prone regions may guide the design of molecules that prevent aggregation. Our analysis revealed that dehydrons can indeed be used to identify aggregation prone regions in proteins. We find that dehydrons in the aggregating proteins occur between highly non-conserved residues, in contrast to their occurrence in highly conserved regions in non-aggregating proteins2. Combining evolutionary conservation and backbone hydration information allowed us to distinguish regions on proteins associated with aggregation from other interaction interfaces. Observations using two proteins (hemoglobin, p53 DNA Binding Domain) will be presented. This novel finding is currently being used to design inhibitors of the p53 aggregation prone mutants.