ABSTRACT
Small angle neutron scattering (SANS) and molecular dynamics (MD) simulations were used to characterize the long-range structuring (aggregation) of aqueous solutions of isopropanol (IPA) and pyridine and the effect on structuring of guanidinium chloride (GdmCl). These solutes serve as highly soluble analogs of the nonpolar aliphatic (IPA) and aromatic (pyridine) side chains of proteins. SANS data showed that isopropanol and pyridine both form clusters in water resulting from interaction between nonpolar groups of the solutes, with pyridine aggregation producing longer-range structuring than isopropanol in 3 m solutions. Addition of GdmCl at 3 m concentration considerably reduced pyridine aggregation but had no effect on isopropanol aggregation. MD simulations of these solutions support the conclusion that long-range structuring involves hydrophobic solute interactions and that Gdm(+) interacts with the planar pyridine group to suppress pyridine-pyridine interactions in solution. Hydrophobic interactions involving the aliphatic groups of isopropanol were unaffected by GdmCl, indicating that the planar and weakly hydrated Gdm(+) cation cannot make productive interactions with the highly curved or "lumpy" aliphatic groups of this solute. These observations support the conclusion that the effects of Gdm(+) ions on protein-stabilizing interactions involving aromatic amino acid side chains make significant contributions to the denaturant activity of GdmCl, whereas interactions with the "lumpy" aliphatic side chains are likely to be less important.
Subject(s)
Amino Acids, Aromatic/chemistry , Guanidine/chemistry , Proteins/chemistry , 2-Propanol/chemistry , Cations/chemistry , Hydrophobic and Hydrophilic Interactions , Molecular Dynamics Simulation , Neutrons , Protein Stability , Pyridines/chemistry , Scattering, Small Angle , Solutions , Water/chemistryABSTRACT
Neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations have been used to characterize the structure of aqueous guanidinium carbonate (Gdm2CO3) solutions. The MD simulations found very strong hetero-ion pairing in Gdm2CO3 solution and were used to determine the best structural experiment to demonstrate this ion pairing. The NDIS experiments confirm the most significant feature of the MD simulation, which is the existence of strong hetero-ion pairing between the Gdm+ and CO3(2-) ions. The neutron structural data also support the most interesting feature of the MD simulation, that the hetero-ion pairing is sufficiently strong as to lead to nanometer-scale aggregation of the ions. The presence of such clustering on the nanometer length scale was then confirmed using small-angle neutron scattering experiments. Taken together, the experiment and simulation suggest a molecular-level explanation for the contrasting denaturant properties of guanidinium salts in solution.
Subject(s)
Electrolytes/chemistry , Guanidine/chemistry , Nanotechnology , Models, Molecular , Solutions , Water/chemistryABSTRACT
We observe the spontaneous formation of path-dependent monodisperse and polydisperse phospholipid unilamellar vesicles (ULV) from two different equilibrium morphologies specifically, disklike micelles and extended lamellae, respectively. On heating beyond a temperature Tc, low temperature disklike micelles, or so-called bicelles, transform into lamellae. Dilution of the lamellar phase, at a fixed temperature, results in a complete unbinding transition and the formation of polydisperse ULV, demonstrating the instability of the lamellar phase. On the other hand, heating of a dilute bicellar phase above Tc results in monodisperse ULV, which on cooling revert back to bicelles for lipid concentrations phi > or = 0.5 wt % and transform into oblate ellipsoids for phi = 0.1 wt %, a morphology not previously seen in "bicellar" lipid mixtures. Monodisperse ULV reform on heating of the oblate ellipsoids.
