Computational Modeling of the Disulfide Cross-Linking Reaction.
J Phys Chem B
; 124(44): 9840-9851, 2020 11 05.
Article
en En
| MEDLINE
| ID: mdl-33111518
ABSTRACT
Disulfide cross-linking is one of the fundamental covalent bonds that exist prevalently in many biological molecules that is involved in versatile functional activities such as antibody stability, viral assembly, and protein folding. Additionally, it is a crucial factor in various industrial applications. Therefore, a fundamental understanding of its reaction mechanism would help gain insight into its different functional activities. Computational simulation of the disulfide cross-linking reaction with hydrogen peroxide (H2O2) was performed at the integrated quantum mechanical/molecular mechanical (QM/MM) level of theory in a water box under periodic boundary conditions. A benchmarking study for the barrier height of the disulfide formation step was performed on a model system between methanethiol and methane sulfenic acid to determine, for the QM system, the best-fit density functional theory (DFT) functional/basis set combination that produces comparable results to a higher-level theory of the coupled-cluster method. Computational results show that the disulfide cross-linking reaction with H2O2 reagent can proceed through a one-step or a two-step pathway for the high pKa cysteines or two different pathways for the low pKa cysteines to ultimately produce the sulfenic acid/sulfenate intermediate complex. Subsequently, those intermediates react with another neutral/anionic cysteine residue to form the cysteine product. In addition, the solvent-assisted proton-exchange/proton-transfer effects were examined on the energetic barriers for the different transition states, and the molecular contributions of the chemically involved water molecules were studied in detail.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Disulfuros
/
Peróxido de Hidrógeno
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Phys Chem B
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos