Despite decades of study, the mechanism by which orotidine-5'-monophosphate decarboxylase (ODCase) catalyzes the decarboxylation of orotidine monophosphate remains unresolved. A computational investigation of the direct decarboxylation mechanism has been performed using mixed quantum mechanical/molecular mechanical (QM/MM) dynamics simulations. The study was performed with the program CP2K that integrates classical dynamics and ab initio dynamics based on the Born-Oppenheimer approach. Two different QM regions were explored. The free energy barriers for decarboxylation of orotidine-5'-monophosphate (OMP) in solution and in the enzyme (using the larger QM region) were determined with the metadynamics method to be 40 kcal/mol and 33 kcal/mol, respectively. The calculated change in activation free energy (ΔΔG ± ) on going from solution to the enzyme is therefore −7 kcal/mol, far less than the experimental change of −23 kcal/mol (for k cat /k uncat Radzicka, A.; Wolfenden, R., Science. 1995, 267, 90-92). These results do not support the direct decarboxylation mechanism that has been proposed for the enzyme. However, in the context of QM/MM calculations, it was found that the size of the QM region has a dramatic effect on the calculated reaction barrier.
O ne of the key issues in biochemistry and molecular modelling is the determination of 3-D minimum-energy configurations (MECs) for macromolecular structures such as proteins and DNA. Steiner minimal trees are seen as a useful algorithmic paradigm for modelling these structures. In this paper, we examine how Steiner minimal trees (SMTs) and the Steiner ratio value comparing minimum spanning trees (MSTs) are correlated with MEC energies in a physically meaningful manner. We conclude that the carbon and nitrogen atoms are Steiner points in the Steiner minimal tree of the proteins.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.