0000000000385386
AUTHOR
Natalia Kanaan
Theoretical study of the temperature dependence of dynamic effects in thymidylate synthase.
A theoretical study of the temperature dependence of dynamic effects in the rate limiting step of the reaction catalyzed by thymidylate synthase is presented in this paper. From hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) optimizations of transition state structures within a fully flexible molecular model, free downhill molecular dynamics trajectories have been performed at four different temperatures. The analysis of the reactive and non-reactive trajectories in the enzyme environment has allowed us to study the geometric and electronic coupling between the substrate, the cofactor and the protein. The results show how the contribution of dynamic effects to the rate enhancement mea…
Application of Grote-Hynes theory to the reaction catalyzed by thymidylate synthase.
A theoretical study of dynamic effects on the rate-limiting step of the thymidylate synthase catalyzed reaction has been carried out by means of Grote-Hynes theory, successfully predicting the values of the recrossing effects for a chemical reaction that involves the transfer of a classical light particle. The transmission coefficients, obtained at 278, 293, 303, and 313 K, are almost invariant and in all cases far from unity, revealing a significant coupling of the environment motions and the reaction coordinate. Nevertheless, their energetic contribution to the activation free energy represents less than 0.50 kcal/mol for each of the four tested temperatures. Calculation of the transmissi…