A Pairwise preferential interaction model for understanding peptide aggregation

A pairwise preferential interaction model (PPIM), based on Kirkwood-Buff integrals, is developed to quantify and characterize the interactions between some of the functional groups commonly observed in peptides. The existing experimental data are analyzed to determine the preferential interaction parameters for different amino acid and small peptide systems in aqueous solutions. The preferential interactions between the different functional groups present in the peptides are then isolated and quantified by assuming simple pairwise additivity. The PPIM approach provides consistent estimates for the pair interactions between the same functional groups obtained from different solute molecules. Furthermore, these interactions appear to be chemically intuitive. It is argued that this type of approach can provide valuable information concerning specific functional group correlations which could give rise to peptide aggregation

Access of ligands to cavities within the core of a protein is rapid.

We have investigated the magnitude and timescale of fluctuations within the core of a protein using the exchange kinetics of indole and benzene binding to engineered hydrophobic cavities in T4 lysozyme. The crystal structures of variant-benzene complexes suggest that relatively large scale fluctuations (1-2 angstrom) of backbone atoms are required for entry of these ligands into the core. Nonetheless, these ligands enter the cavities rapidly, with bimolecular rate constants of approximately 10(6)-10(7) M(-1) s(-1) and a low activation barrier, 2-5 kcal mol(-1). These results suggest that protein cores undergo substantial fluctuations on the millisecond to microsecond timescale and that entry of small molecules into protein interiors is not strongly limited by steric occlusion

Water activity and osmotic coefficients in solutions of glycine, glutamic acid, histidine and their salts at 298.15 K and 310.15 K

From vapor pressure osmometry data, the activity of water, osmotic coeffs. and mean ionic activity coeffs. of glycine (m = 0.006-3.2 mol/kg-1), L-histidine (m = 0.005-0.23 mol/kg-1), L-histidine monohydrochloride (m = 0.008-0.63 mol/kg-1), glutamic acid (m = 0.004-0.05 mol/kg-1), sodium L-glutamate (m = 0.007-0.6 mol/kg-1), and calcium L-glutamate (m = 0.008-0.6 mol/kg-1) have been obtained in aq. solns. at 298.15 and 310.15 K. The Pitzer equations and the mean spherical approxn. (MSA) are used for theor. modeling