Computational Approaches to Investigate and Design Lipid-binding Domains for Membrane Biosensing

Association of proteins with cellular membranes is critical for signaling and membrane trafficking processes. Many peripheral lipid-binding domains have been identified in the last few decades and have been investigated for their specific lipid-sensing properties using traditional in vivo and in vitro studies.  However, several knowledge-gaps remain owing to intrinsic limitations of these methodologies. Thus, novel approaches are necessary to further our understanding in lipid-protein biology. This review briefly discusses lipid binding domains that act as specific lipid biosensors and provides a broad perspective on the computational approaches such as molecular dynamics (MD) simulations and machine learning (ML)-based techniques that can be used to study protein-membrane interactions. We also highlight the need for de novo design of proteins that elicit specific lipid binding properties.