title: Taste of sugar at the membrane: thermodynamics and kinetics of the interaction of a disaccharide with lipid bilayers.
abstract: Sugar recognition at the membrane is critical in various physiological processes. Many aspects of sugar-membrane interaction are still unknown. We take an integrated approach by combining conventional molecular-dynamics simulations with enhanced sampling methods and analytical models to understand the thermodynamics and kinetics of a di-mannose molecule in a phospholipid bilayer system. We observe that di-mannose has a slight preference to localize at the water-phospholipid interface. Using umbrella sampling, we show the free energy bias for this preferred location to be just -0.42 kcal/mol, which explains the coexistence of attraction and exclusion mechanisms of sugar-membrane interaction. Accurate estimation of absolute entropy change of water molecules with a two-phase model indicates that the small energy bias is the result of a favorable entropy change of water molecules. Then, we incorporate results from molecular-dynamics simulation in two different ways to an analytical diffusion-reaction model to obtain association and dissociation constants for di-mannose interaction with membrane. Finally, we verify our approach by predicting concentration dependence of di-mannose recognition at the membrane that is consistent with experiment. In conclusion, we provide a combined approach for the thermodynamics and kinetics of a weak ligand-binding system, which has broad implications across many different fields.
authors: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
authors: Jianhui
authors: J
authors: Tian
authors: Anurag
authors: A
authors: Sethi
authors: Basil I
authors: BI
authors: Swanson
authors: Byron
authors: B
authors: Goldstein
authors: S
authors: S
authors: Gnanakaran
mesh_terms: D004187:Disaccharides / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008358:Mannose / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D004187:Disaccharides; D008051:Lipid Bilayers; D008055:Lipids; D014867:Water; D008358:Mannose