Analysis of protein-protein interactions by identification and investigation of the interfacial cores
PI: J. Liu (Department of Computer and Information Science, IUPUI)
Protein-protein interactions are important for biological
functions, and aberrant protein-protein interaction events can cause
diseases such as cancer and diabetes. However, how proteins recognize
each other and form stable complexes is not fully understood. Protein
homodimers are association between two identical protein chains and can
be considered the simplest form of protein-protein interactions. In
this application, we propose to test the hypothesis that the
interfacial core which consists of the most buried amino acids, likely
serves as the seeding site for strong hydrophobic interactions which
has been recognized as the driving forces for protein association.
Static properties such as hydrophobicity and dynamic properties such as
stability and water-exchange rate can be the key features and
prerequisite for stable protein-protein interactions. The outcome of
this study will help us understand the principle question of how
protein recognizes each other. It can further help identify critical
residues that can be selected as targeting site to disrupt or enhance
protein-protein interaction in drug discovery. If successfully
accomplished, the findings will have significant impact on drug
discovery and accelerate drug discovery process.
