Theoretical study of mechanisms for the hydrolytic deamination of cytosine via steered molecular dynamic simulations.

ABSTRACT: Gibbs free energy profiles of the cytosine deamination assisted by a water molecule in a discrete aqueous medium were obtained by the application of Steered Molecular Dynamic (SMD) simulations. Two pathways were considered to explain the mechanism of this process, where the water molecule attacks the C-N bond to give an intermediate (an amino-hydroxy-oxo structure in the A-path, and a hydroxy-oxo in the B-path) as the determinant step of reaction. Stationary structures along both energy profiles were analyzed at molecular dynamics level, obtaining states with higher free energies than those from electronic calculations in the gas phase and in solution described as a continuous medium. From the results obtained, the more complex A-pathway, with five steps, was kinetically the most favorable

SUBMITTER: Tolosa S 

PROVIDER: S-EPMC9087476 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature