Modeling membrane geometries implicitly in Rosetta
Year: 2024
Type: article
Abstract: Interactions between membrane proteins (MPs) and lipid bilayers are critical for many cellular functions. In the Rosetta molecular modeling suite, the implicit membrane energy function is based on a "slab" model, which represent the membrane as a flat bilayer. However, in nature membranes often have a curvature that is important for function and/or stability. Even more prevalent, in structural biology research MPs are reconstituted in model membrane systems such as micelles, bicelles, nanodiscs, or liposomes. Thus, we have modified the existing membrane energy potentials within the RosettaMP framework to allow users to model MPs in different membrane geometries. We show that these modifications can be utilized in core applications within Rosetta such as structure refinement, protein-protein docking, and protein design. For MP structures found in curved membranes, refining these structures in curved, implicit membranes produces higher quality models with structures closer to experimentally determined structures. For MP systems embedded in multiple membranes, representing both membranes results in more favorable scores compared to only representing one of the membranes. Modeling MPs in geometries mimicking the membrane model system used in structure determination can improve model quality and model discrimination.
Source: Protein Science
DOI: 10.1002/pro.4908
Authors: Hope Woods, Julia Koehler Leman, Jens Meiler
Institutions: Vanderbilt University, Flatiron Institute, Leipzig University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,270
OpenAlex ID: W4391847155