Molecular interpretation of preferential interactions in protein solvation: a solvent-shell perspective by means of minimum-distance distribution functions

TY - JOUR

T1 - Molecular interpretation of preferential interactions in protein solvation

T2 - a solvent-shell perspective by means of minimum-distance distribution functions

AU - Martinez, Leandro

AU - Shimizu, Seishi

N1 - © 2017 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2017/12/12

Y1 - 2017/12/12

N2 - Preferential solvation is a fundamental parameter for the interpretation of solubility and solute structural stability. The molecular basis for solute-solvent interactions can be obtained through distribution functions, and the thermodynamic connection to experimental data depends on the computation of distribution integrals, specically Kirkwood-Bu integrals for the determination of preferential interaction or exclusion. Standard radial distribution function functions, however, are not convenient for the study of the solvation of complex, non-spherical solutes, as proteins structures. Here we show that minimum-distance distribution functions can be used to compute KB integrals while at the same time providing a rich view of solute-solvent interactions at the molecular level. We compute preferential solvation parameters for Ribonuclease T1 in aqueous solutions of urea and trimethylamine N-oxide (TMAO), and show that, while macroscopic solvation shows that urea is preferentially bound to the protein surface and TMAO is preferentially excluded, both display specic density augmentations at the protein surface. Therefore, direct protein-osmolyte interactions can play a role in the stability and activity of the protein even for preferentially hydrated systems. The generality of the distribution function and its natural connection to thermodynamic data suggests that it will be useful in general for the study of solvation in mixtures of structurally complex solutes and solvents.

AB - Preferential solvation is a fundamental parameter for the interpretation of solubility and solute structural stability. The molecular basis for solute-solvent interactions can be obtained through distribution functions, and the thermodynamic connection to experimental data depends on the computation of distribution integrals, specically Kirkwood-Bu integrals for the determination of preferential interaction or exclusion. Standard radial distribution function functions, however, are not convenient for the study of the solvation of complex, non-spherical solutes, as proteins structures. Here we show that minimum-distance distribution functions can be used to compute KB integrals while at the same time providing a rich view of solute-solvent interactions at the molecular level. We compute preferential solvation parameters for Ribonuclease T1 in aqueous solutions of urea and trimethylamine N-oxide (TMAO), and show that, while macroscopic solvation shows that urea is preferentially bound to the protein surface and TMAO is preferentially excluded, both display specic density augmentations at the protein surface. Therefore, direct protein-osmolyte interactions can play a role in the stability and activity of the protein even for preferentially hydrated systems. The generality of the distribution function and its natural connection to thermodynamic data suggests that it will be useful in general for the study of solvation in mixtures of structurally complex solutes and solvents.

U2 - 10.1021/acs.jctc.7b00599

DO - 10.1021/acs.jctc.7b00599

M3 - Article

SN - 1549-9618

VL - 13

SP - 6358

EP - 6372

JO - Journal of chemical theory and computation

JF - Journal of chemical theory and computation

IS - 12

ER -