(225e) A New High-Throughput Computational Method to Generate Energy Profile of Integral Membrane Protein-Protein Association

Integral membrane proteins play a key role in crucial biological events including neurotransmission, signaling cascade, immune response, and cancer metastasis among others. Not surprisingly, these membrane proteins represent 20-30% of the proteome of most organisms. Despite their significance, isolation and characterization of membrane proteins is experimentally challenging due to their hydrophobic membrane environment. Several computational (docking and self-assembly) methods to study protein assembly have been developed but have limited scope or affordability. There is growing need for a comprehensive and affordable method that captures molecular-level detail of protein association in complex lipid environments. Here we report the development of a new method that provides qualitative and quantitative estimates of membrane protein association to generate a comprehensive Protein Association Energy Landscape (PANEL). The PANEL method is a computationally inexpensive approach to generating energy profiles for a wide range of proteins belonging to diverse set of species in variable membrane environments. We have used our approach to show association of membrane proteins that are responsible for the selectivity of the blood-brain tight junctions.