Computational modeling of biomolecular systems: Molecular mechanism of membrane binding of peripheral membrane proteins.

摘要

Peripheral membrane targeting proteins play essential roles in numerous cellular trafficking and signaling pathways. At the molecular level, the interactions between lipids and protein side chains at the binding interfaces drive the membrane targeting. High-resolution techniques to describe the structure and dynamics of protein-membrane complex are valuable, however, detailed mechanistic analysis of membrane targeting events remains a great challenge. Molecular dynamics (MD) simulations have proven to be a useful tool in revealing molecular-level details at the binding interfaces. This thesis will describe the use of MD simulations, in some cases with experimental inputs, to investigate molecular membrane binding mechanisms for three biologically relevant peripheral membrane protein systems, including epsin N-terminal homology (ENTH), general receptor for phosphoinositides 1 (GRP1) PH, protein kinase C alpha (PKCα) C2 domains.