Dataset Information

Theoretical Study of Adenine to Guanine Transition Assisted by Water and Formic Acid Using Steered Molecular Dynamic Simulations.

ABSTRACT: The free energy profile of the adenine to guanine transition in the gas and aqueous phases was obtained by applying steered molecular dynamic (SMD) simulations. Three processes were considered to explain the mechanism assisted by water and formic acid molecules. The first process is hydrolytic deamination of adenine, then oxidation of the hypoxanthine previously formed, and finally, the animation from xanthine to guanine. In the gas phase these processes indicate a slow and not spontaneous conversion (?G g = 4.07 kcal·mol-1, k = 5.59·10-40 s-1), and a lifetime for guanine of ? = 7.75·10+22 s. The presence of solvent makes the transition more difficult by increasing the reaction energy to 26.90 kcal·mol-1 and decreasing the speed of the process to 1.63·10-55 s-1. However, it decreases the energy of the deamination process to -9.63 kcal·mol-1 and the lifetime of guanine base to ? = 6.85·10+17 s when the surrounding medium used in the transition process is aqueous. The results show that the guanine could participate in genetic mutations based on the lifetimes obtained. Transition states and intermediates structures were analyzed at the molecular dynamic level. This allows to follow the mechanism over time and to calculate thermodynamic and kinetic properties.

SUBMITTER: Tolosa S

PROVIDER: S-EPMC6582222 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Theoretical Study of Adenine to Guanine Transition Assisted by Water and Formic Acid Using Steered Molecular Dynamic Simulations.

Tolosa Santiago S Sansón Jorge A JA Hidalgo Antonio A

Frontiers in chemistry 20190612

The free energy profile of the adenine to guanine transition in the gas and aqueous phases was obtained by applying steered molecular dynamic (SMD) simulations. Three processes were considered to explain the mechanism assisted by water and formic acid molecules. The first process is hydrolytic deamination of adenine, then oxidation of the hypoxanthine previously formed, and finally, the animation from xanthine to guanine. In the gas phase these processes indicate a slow and not spontaneous conve ...[more]

PMID: 31249828

Similar Datasets

Project description:Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P) from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD) simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon stretching.

Dataset Information

Theoretical Study of Adenine to Guanine Transition Assisted by Water and Formic Acid Using Steered Molecular Dynamic Simulations.

Publications

Theoretical Study of Adenine to Guanine Transition Assisted by Water and Formic Acid Using Steered Molecular Dynamic Simulations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets