title: Refining the treatment of membrane proteins by coarse-grained models.
abstract: Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, 90089-1062.
authors.forename: Igor
authors.initials: I
authors.lastname: Vorobyov
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, 90089-1062.
authors.forename: Ilsoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, 90089-1062.
authors.forename: Zhen T
authors.initials: ZT
authors.lastname: Chu
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, 90089-1062.
authors.forename: Arieh
authors.initials: A
authors.lastname: Warshel
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry; D030562:Databases, Protein; D004926:Escherichia coli / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D054466:Phospholipases A1 / Q000737:chemistry; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D001425:Bacterial Outer Membrane Proteins; D008565:Membrane Proteins; D054466:Phospholipases A1; C412876:outer membrane phospholipase A
keywords: OmpLA; arginine; folding energy; ion-induced defect; lipid membrane; membrane electrostatics; molecular modeling; mutation; partitioning free energy; rotamer