Kirkwood-Buff-Derived Alcohol Parameters for Aqueous Carbohydrates and Their Application to Preferential Interaction Coefficient Calculations of Proteins.
J Phys Chem B
; 122(40): 9350-9360, 2018 10 11.
Article
em En
| MEDLINE
| ID: mdl-30216067
ABSTRACT
The CHARMM36 carbohydrate parameter set did not adequately reproduce experimental thermodynamic data of carbohydrate interactions with water or proteins or carbohydrate self-association; thus, a new nonbonded parameter set for carbohydrates was developed. The parameters were developed to reproduce experimental Kirkwood-Buff integral values, defined by the Kirkwood-Buff theory of solutions, and applied to simulations of glycerol, sorbitol, glucose, sucrose, and trehalose. Compared to the CHARMM36 carbohydrate parameters, these new Kirkwood-Buff-based parameters reproduced accurately carbohydrate self-association and the trend of activity coefficient derivative changes with concentration. When using these parameters, preferential interaction coefficients calculated from simulations of these carbohydrates and the proteins lysozyme, bovine serum albumin, α-chymotrypsinogen A, and RNase A agreed well with the experimental data, whereas use of the CHARMM36 parameters indicated preferential inclusion of carbohydrates, in disagreement with the experiment. Thus, calculating preferential interaction coefficients from simulations requires using a force field that accurately reproduces trends in the thermodynamic properties of binary excipient-water solutions, and in particular the trend in the activity coefficient derivative. Finally, the carbohydrate-protein simulations using the new parameters indicated that the carbohydrate size was a major factor in the distribution of different carbohydrates around a protein surface.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Álcoois Açúcares
/
Proteínas
/
Açúcares
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Phys Chem B
Ano de publicação:
2018
Tipo de documento:
Article