Journal
JOURNAL OF PHYSICAL CHEMISTRY B
Volume 114, Issue 8, Pages 3020-3027Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jp910340t
Keywords
-
Categories
Ask authors/readers for more resources
Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational method combines high-precision density functional theory (DFT) calculations performed on the core of the reactant system with classical mechanical free energy evaluations based on the sampling of the configuration space of reaction environment. The predicted reaction energy barriers are in satisfactory agreement with experimental data, proving that the present method provides a reliable description of the mechanism of reaction. The role of the protein environment in this mechanism is further emphasized by analyzing the different contributions to the free energy profiles. It is shown that the protein environment affects the reaction by three factors: polarizability, steric hindrance of the reactant site, and S-S bridge distortion due to structural constraints. The corresponding effects are quantitatively evaluated, and the results are discussed in connection with the current two-step reaction model for the reduction of S-S bridges in proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available