4 research outputs found
Correlation between sequence hydrophobicity and surface-exposure pattern of database proteins
Hydrophobicity is thought to be one of the primary forces driving the folding
of proteins. On average, hydrophobic residues occur preferentially in the core,
whereas polar residues tends to occur at the surface of a folded protein. By
analyzing the known protein structures, we quantify the degree to which the
hydrophobicity sequence of a protein correlates with its pattern of surface
exposure. We have assessed the statistical significance of this correlation for
several hydrophobicity scales in the literature, and find that the computed
correlations are significant but far from optimal. We show that this less than
optimal correlation arises primarily from the large degree of mutations that
naturally occurring proteins can tolerate. Lesser effects are due in part to
forces other than hydrophobicity and we quantify this by analyzing the surface
exposure distributions of all amino acids. Lastly we show that our database
findings are consistent with those found from an off-lattice hydrophobic-polar
model of protein folding.Comment: 16 pages, 2 tables, 8 figure
Kosmotropes and chaotropes: modelling preferential exclusion, binding and aggregate stability
Kosmotropic cosolvents added to an aqueous solution promote the aggregation
of hydrophobic solute particles, while chaotropic cosolvents act to destabilise
such aggregates. We discuss the mechanism for these phenomena within an adapted
version of the two-state Muller-Lee-Graziano model for water, which provides a
complete description of the ternary water/cosolvent/solute system for small
solute particles. This model contains the dominant effect of a kosmotropic
substance, which is to enhance the formation of water structure. The consequent
preferential exclusion both of cosolvent molecules from the solvation shell of
hydrophobic particles and of these particles from the solution leads to a
stabilisation of aggregates. By contrast, chaotropic substances disrupt the
formation of water structure, are themselves preferentially excluded from the
solution, and thereby contribute to solvation of hydrophobic particles. We use
Monte Carlo simulations to demonstrate at the molecular level the preferential
exclusion or binding of cosolvent molecules in the solvation shell of
hydrophobic particles, and the consequent enhancement or suppression of
aggregate formation. We illustrate the influence of structure-changing
cosolvents on effective hydrophobic interactions by modelling qualitatively the
kosmotropic effect of sodium chloride and the chaotropic effect of urea.Comment: 13 pages, 12 figures; inclusion of review material, parameter
analysis and comparison of kosmotropic and chaotropic effect