title: Extension of the Highly Mobile Membrane Mimetic to Transmembrane Systems through Customized in Silico Solvents.
abstract: The mechanics of the protein-lipid interactions of transmembrane proteins are difficult to capture with conventional atomic molecular dynamics, due to the slow lateral diffusion of lipids restricting sampling to states near the initial membrane configuration. The highly mobile membrane mimetic (HMMM) model accelerates lipid dynamics by modeling the acyl tails nearest to the membrane center as a fluid organic solvent while maintaining an atomic description of the lipid headgroups and short acyl tails. The HMMM has been applied to many peripheral protein systems; however, the organic solvent used to date caused deformations in transmembrane proteins by intercalating into the protein and disrupting interactions between individual side chains. We ameliorate the effect of the solvent on transmembrane protein structure through the development of two new in silico Lennard-Jones solvents. The parameters for the new solvents were determined through an extensive parameter search in order to match the bulk properties of alkanes in a highly simplified model. Using these new solvents, we substantially improve the insertion free energy profiles of 10 protein side chain analogues across the entire bilayer. In addition, we reduce the intercalation of solvent into transmembrane systems, resulting in native-like transmembrane protein structures from five different topological classes within a HMMM bilayer. The parametrization of the solvents, in addition to their computed physical properties, is discussed. By combining high lipid lateral diffusion with intact transmembrane proteins, we foresee the developed solvents being useful to efficiently identify membrane composition inhomogeneities and lipid binding caused by the presence of membrane proteins.
authors.affiliation: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Josh V
authors.initials: JV
authors.lastname: Vermaas
authors.affiliation: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Department of Chemistry, School of Chemical Sciences, National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Taras V
authors.initials: TV
authors.lastname: Pogorelov
authors.affiliation: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Department of Biochemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
mesh_terms: D003198:Computer Simulation; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D008055:Lipids; D008565:Membrane Proteins; D012997:Solvents