Computer simulations have proven to be very useful for the study of the structuring of complex solutions, providing information difficult or impossible to obtain by experimental means. 'While this level of detail is one of the great advantages of Molecular Mechanics (MM) calculations, there is an obvious and growing necessity to validate the results of such simulations by a demanding comparison with experiment. The objective of the studies proposed here will be to use MM simulations to model the solvent structuring imposed on water by complex biological solutes, and then for comparison, to measure this structuring for the same molecules using first difference isotopic substitution neutron diffraction experiments. The molecules to be studied will be various pentose and hexose sugars, because of their practical experimental advantages over the peptides, their overall biological importance, and their usefulness as more general models for biopolymer hydration. The sugar molecules to be studied will be prepared synthetically, with only single and double isotopic substitutions at specific positions, in order to eliminate the loss in detail due to averaging over different environments when using multiply-labeled solutes. The collective structure which solutes impose upon solvent water plays a profound role in many biological processes, such as protein folding, membrane formation, and the binding of ligands to proteins. Such structuring is often invoked to explain all manners of phenomena, but without any definitive way to actually probe this structure or specify its detailed relationship to the solute topology. Molecular Dynamics simulations offer an ideal way to study this structuring on the molecular level, but in general there have been few ways to compare the calculated results with experiment. The principal experimental technique for probing liquid structure is neutron diffraction, which has been very successful in determining the structures of electrolyte solutions and solutions of simple solutes such as rare gases. Unfortunately, the averaging over all like atoms obscures anisotropic structuring details in more complex solutes. The proposed project will use synthetic methods to prepare sugar molecules singly substituted with deuterium or 13C at specific positions, and double substitutions with one atom each of D and 13C, exploiting the overlapping rdfs to probe the anisotropy in the solvent distribution. The radial distribution function for these individual atoms will then be compared with those calculated from new MD simulations of these sugars at the same high experimental concentrations.
| Schnupf, Udo; Brady, John W (2017) Water structuring above solutes with planar hydrophobic surfaces. Phys Chem Chem Phys 19:11851-11863 |
| Mason, Philip E; Neilson, George W; Saboungi, Marie-Louise et al. (2013) The conformation of a ribose derivative in aqueous solution: a neutron-scattering and molecular dynamics study. Biopolymers 99:739-45 |
| Tavagnacco, Letizia; Brady, John W; Cesàro, Attilio (2013) The Interaction of Sorbitol with Caffeine in Aqueous Solution. Food Biophys 8:216-222 |
| Mason, Philip E; Neilson, George W; Price, David L et al. (2013) A new structural technique for examining ion-neutral association in aqueous solution. Faraday Discuss 160:161-70; discussion 207-24 |
| Chen, Mo; Bomble, Yannick J; Himmel, Michael E et al. (2012) Molecular dynamics simulations of the interaction of glucose with imidazole in aqueous solution. Carbohydr Res 349:73-7 |
| Brady, John W; Tavagnacco, Letizia; Ehrlich, Laurent et al. (2012) Weakly hydrated surfaces and the binding interactions of small biological solutes. Eur Biophys J 41:369-77 |
| Tavagnacco, Letizia; Engstrom, Olof; Schnupf, Udo et al. (2012) Caffeine and sugars interact in aqueous solutions: a simulation and NMR study. J Phys Chem B 116:11701-11 |
| Mason, Phillip E; Lerbret, Adrien; Saboungi, Marie-Louise et al. (2011) Glucose interactions with a model peptide. Proteins 79:2224-32 |
| Mason, Philip E; Neilson, George W; Price, David et al. (2011) Simulation and Neutron Diffraction Studies of Small Biomolecules in Water. Food Biophys 6:210-216 |
| Tavagnacco, Letizia; Schnupf, Udo; Mason, Philip E et al. (2011) Molecular dynamics simulation studies of caffeine aggregation in aqueous solution. J Phys Chem B 115:10957-66 |
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