Understanding Periperal Membrane Protein Interactions | BPS Thematic Meeting

Understanding Peripheral Membrane Protein Interactions: Structure, Dynamics, Function and Therapy

Monday Speaker Abstracts

MODELLING LIPID INTERACTIONS AT MEMBRANE INTERFACES WITH MEMPRO AND CCD2MD Phillip J. Stansfeld ; 1 University of Warwick, Coventry, United Kingdom Peripheral membrane proteins are critical regulators of membrane dynamics, often mediating curvature, lipid organization, and protein recruitment at the membrane interface. To investigate these proteins, we have developed two new computational tools specifically designed for the study of peripheral membrane interactions. MemPrO is a predictive method that identifies membrane-binding interfaces and orientations of peripheral proteins, enabling rapid screening of potential membrane-contacting regions. In parallel, we have developed CCD2MD, a flexible pipeline for setting up molecular dynamics simulations involving protein-lipid interactions and post-translational lipid modifications, using structural predictions from AlphaFold3, Chai, or Boltz. CCD2MD supports both coarse-grained and atomistic simulations, making it particularly well-suited for modeling complex membrane environments and peripheral protein behavior. As an exemplar system, we have studied the membrane interactions of MreB, a bacterial actin homolog. MreB binds the cytoplasmic leaflet of the E. coli inner membrane and remodels its architecture. Our molecular dynamics simulations show that MreB filaments recruit the cone shaped lipid cardiolipin and induce membrane bending toward the periplasmic space. This effect is cardiolipin concentration-dependent and is mediated by specific residues (R105 and R136), as well as the N-terminal amphipathic helix. These findings reveal a dual mechanism of membrane remodeling by MreB: lipid recruitment and physical distortion. The case of MreB illustrates how peripheral membrane proteins can exert both mechanical and chemical influence on membrane architecture. Our newly developed methods provide a generalizable framework for exploring similar mechanisms across a wide range of membrane-associated systems.

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