Up until now, it has remained elusive as to why the flavin prenyltransferase UbiX requires dimethylallyl monophosphate (DMAP) as one of its cosubstrates instead of dimethylallyl pyrophosphate (DMAPP), even though the former is not used in metabolic pathways, while the latter is a common isoprenoid precursor. Herein, mainly on the basis of molecular dynamics (MD) simulations, we demonstrate that the selectivity of UbiX may be governed by its conformational dynamics. The hydrogen-bonding network of UbiX does not facilitate a proper encompassing of DMAPP. This induces significant conformational changes of the enzyme that result mostly in unreactive trajectories, whereas DMAP remains at a catalytically competent position throughout the performed simulations. Within the presented study, we provide a justification for the atypical selectivity of UbiX.
Herein, we present a combined (experimental and computational) study of the Finkelstein reaction in condensed phase, where bromine is substituted by iodine in 2-bromoethylbenzene, in the presence of either acetone or acetonitrile as a solvent. Performance of various density functional theory and ab initio methods were tested for reaction barrier heights as well as for bromine and carbon kinetic isotope effects (KIEs). Two different implicit solvation models were examined (PCM and SMD). Theoretically predicted KIEs were compared with experimental values, while reaction barrier heights were assessed using the CCSD(T)-level and experimental energies as reference. In general, although the tested parameters (energies and KIEs) do not exhibit any substantial difference upon a change of the solvent, the different behavior of the theoretical methods was observed depending on the solvent. With respect to isotope effects, both PCM and SMD seem to perform very similarly, though results obtained with PCM are slightly closer to the experimental values. For predicting reaction barriers, utilization of either PCM or SMD solvation models yielded different results. Functionals from the ωB97 family: ωB97, ωB97X, and ωB97X-D provide the most accurate results for the studied system.
Herein we present the results of an in-depth simulation study of LinA and its two variants. In our analysis, we combined the exploration of protein conformational dynamics with and without bound substrates (hexachlorocyclohexane (HCH) isomers) performed using molecular dynamics simulation followed by the extraction of the most frequently visited conformations and their characteristics with a detailed description of the interactions taking place in the active site between the respective HCH molecule and the first shell residues by using symmetry-adapted perturbation theory (SAPT) calculations. A detailed investigation of the conformational space of LinA substates has been accompanied by description of enzymatic catalytic steps carried out using a hybrid quantum mechanics/molecular mechanics (QM/MM) potential along with the computation of the potential of mean force (PMF) to estimate the free energy barriers for the studied transformations: dehydrochlorination of γ-, (−)-α-, and (+)-α-HCH by LinA-type I and -type II variants. The applied combination of computational techniques allowed us not only to characterize two LinA types but also to point to the most important differences between them and link their features to catalytic efficiency each of them possesses toward the respective ligand. More importantly it has been demonstrated that type I protein is more mobile, its active site has a larger volume, and the dehydrochlorination products are stabilized more strongly than in the case of type II enzyme, due to differences in the residues present in the active sites. Additionally, interaction energy calculations revealed very interesting patterns not predicted before but having the potential to be utilized in any attempts of improving LinA catalytic efficiency. On the basis of all these observations, LinA-type I protein seems to be more preorganized for the dehydrochlorination reaction it catalyzes than the type II variant.
Streszczenie: Otrzymano mieszanki kauczuków butadienowo-akrylonitrylowego (NBR) i butadienowo--styrenowego (SBR) z tritlenkiem antymonu (5-20 phr) i stabilnymi termicznie pigmentami -ftalocyjani-n¹ cynkow¹ oraz ftalocyjanin¹ chloroglinow¹, nastêpnie je sieciowano za pomoc¹ siarkowego uk³adu sie-ciuj¹cego. Badano wp³yw jednoczesnego zastosowania w mieszance kauczukowej Sb 2 O 3 i pochodnych ftalocyjaniny na stabilnooeae termiczn¹, palnooeae, zagro¿enie po¿arowe i w³aoeciwooeci mechaniczne uzyskanych wulkanizatów. Stwierdzono, ¿e wytworzone materia³y elastomerowe wykazywa³y mniejsz¹ palnooeae, mniejsze zagro¿enie po¿arowe i wiêksz¹ odpornooeae termiczn¹ oraz charakteryzowa³y siê lepszymi w³aoeciwooeciami mechanicznymi ni¿ niezabarwione wulkanizaty niezawieraj¹ce tritlenku amonu.
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.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.