Evidence for microscopic, long-range hydration forces for a hydrophobic amino acid

We have combined neutron solution scattering experiments with molecular dyn amics simulation to isolate an excess experimental signal that is caused so lely by N-acetyl-leucine-amide (NALA) correlations in aqueous solution. Thi s excess signal contains information about how NALA molecule centers are co rrelated in water, and we show how these solute-solute correlations might b e determined at dilute concentrations in the small angle region, We have te sted qualitatively different pair distribution functions for NALA molecule centers-gas, cluster, and aqueous forms of g(c)(r)-and have found that the excess experimental signal is adequate enough to rule out gas and cluster p air distribution functions. The aqueous form of g(c)(r) that exhibits a sol vent-separated minimum, and possibly longer-ranged correlations as well, is not only physically sound but reproduces the experimental data reasonably well. This work demonstrates that important information in the small angle region can be mined to resolve solute-solute correlations, their lengthscal es, and thermodynamic consequences even at dilute concentrations. The hydra tion forces that operate on the microscopic scale of individual amino acid side chains, implied by the small angle scattering data, could have signifi cant effects on the early stages of protein folding, on ligand binding, and on other intermolecular interactions.