title: Highly Coarse-Grained Representations of Transmembrane Proteins.
abstract: Numerous biomolecules and biomolecular complexes, including transmembrane proteins (TMPs), are symmetric or at least have approximate symmetries. Highly coarse-grained models of such biomolecules, aiming at capturing the essential structural and dynamical properties on resolution levels coarser than the residue scale, must preserve the underlying symmetry. However, making these models obey the correct physics is in general not straightforward, especially at the highly coarse-grained resolution where multiple (∼3-30 in the current study) amino acid residues are represented by a single coarse-grained site. In this paper, we propose a simple and fast method of coarse-graining TMPs obeying this condition. The procedure involves partitioning transmembrane domains into contiguous segments of equal length along the primary sequence. For the coarsest (lowest-resolution) mappings, it turns out to be most important to satisfy the symmetry in a coarse-grained model. As the resolution is increased to capture more detail, however, it becomes gradually more important to match modular repeats in the secondary structure (such as helix-loop repeats) instead. A set of eight TMPs of various complexity, functionality, structural topology, and internal symmetry, representing different classes of TMPs (ion channels, transporters, receptors, adhesion, and invasion proteins), has been examined. The present approach can be generalized to other systems possessing exact or approximate symmetry, allowing for reliable and fast creation of multiscale, highly coarse-grained mappings of large biomolecular assemblies.
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Jesper J
authors.identifier: http://orcid.org/0000-0003-1411-9080
authors.initials: JJ
authors.lastname: Madsen
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Anton V
authors.initials: AV
authors.lastname: Sinitskiy
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Jianing
authors.identifier: http://orcid.org/0000-0002-0143-8894
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Gregory A
authors.identifier: http://orcid.org/0000-0002-3267-6748
authors.initials: GA
authors.lastname: Voth
mesh_terms: D007536:Isomerism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D008565:Membrane Proteins