Prospects of Ocimum Gratissimum Linn. (Lamiaceae) to Control Exorista SorbillansWiedemann (Diptera: Tachinidae) Menace of Silkworm in Seriecosystem

Tachinid parasitoids are in focus mostly as biocontrol agents to be released against lepidopteran pest. But surprisingly certain tachinid parasitoids attack economically beneficial insects like silkworm and demands control measures against them. The uzi fly Exoristasorbillans (Diptera: Tachinidae) infests all commercially important silkworm species including Antheraeaassamensis where it causes upto 80 percent crop loss. The control of such parasitoids is a difficult task as the larval stage is endoparasitic and chemical insecticides do not reach the targeted parasitoid without exposing the silkworm host.In the present study,we evaluated adulticidal activity of different solvent extracts and essential oil of Ocimumgratissimum. We found higher efficacy of essential oil in comparison to other solvent extracts. The effective fraction of oil was found to contain thymol or its isomer carvacrol as the major compound in GC-MS studies. Finally, O. gratissimum oil-based combination (MI) and carvacrol based combination of essential oil compounds (MII) were prepared, tested and found to be effective against the fly. In silico positive interaction of essential oil compounds with acetylcholinesterase enzyme model of the fly revealed that the said enzyme is one of the target proteins for these oil compounds to interrupt its function and subsequent lethal action.

Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase

The enzyme model, mouse acetylcholinesterase, which exhibits its active site at the bottom of a narrow gorge, was investigated in the presence of different concentrations of sucrose to shed light on the protein and water dynamics in cholinesterases. The study was conducted by incoherent neutron scattering, giving access to molecular dynamics within the time scale of sub-nano to nanoseconds, in comparison with molecular dynamics simulations. With increasing sucrose concentration, we found non-linear effects, e.g., first a decrease in the dynamics at 5 wt% followed by a gain at 10 wt% sucrose. Direct comparisons with simulations permitted us to understand the following findings: at 5 wt%, sugar molecules interact with the protein surface through water molecules and damp the motions to reduce the overall protein mobility, although the motions inside the gorge are enhanced due to water depletion. When going to 10 wt% of sucrose, some water molecules at the protein surface are replaced by sugar molecules. By penetrating the protein surface, they disrupt some of the intra-protein contacts, and induce new ones, creating new pathways for correlated motions, and therefore, increasing the dynamics. This exhaustive study allowed for an explanation of the detail interactions leading to the observed non-linear behavior.

Prediction of Michaelis constants from structural features using deep learning

ABSTRACTThe Michaelis constant KM describes the affinity of an enzyme for a specific substrate, and is a central parameter in studies of enzyme kinetics and cellular physiology. As measurements of KM are often difficult and time-consuming, experimental estimates exist for only a minority of enzyme-substrate combinations even in model organisms. Here, we build and train an organism-independent model that successfully predicts KM values for natural enzyme-substrate combinations using machine and deep learning methods. Predictions are based on a task-specific molecular fingerprint of the substrate, generated using a graph neural network, and the domain structure of the enzyme. Model predictions can be used to estimate enzyme efficiencies, to relate metabolite concentrations to cellular physiology, and to fill gaps in the parameterization of kinetic models of cellular metabolism.

Penambatan Molekuler dan Simulasi Dinamika Molekuler Senyawa Dari Genus Nigella Terhadap Penghambatan Aktivitas Enzim Protease HIV-1

Nigella plant genus has potential as anti-HIV. One species of Nigella, Nigella sativa has been reported to have HIV-1 protease enzyme inhibitory activity. This research aims to determine the compounds of the Nigella genus that have activity as HIV-1 protease enzyme inhibitory activity through molecular docking method by Autodock Vina and to compare interaction stability through molecular dynamics simulations by AMBER. The metabolite of the Nigella genus was obtained from the KnapSack website, and enzyme model was obtained from the Protein Data Bank (3NU3). The results of molecular docking found the lowest affinity energy of Nigella compound is Nigellidine 4-O-sulfite (-13.4 kcal/mol). Meanwhile, the affinity energy of the ligand native (Amprenavir) was -12.1 kcal/mol. The lowest affinity energy of Nigellidine 4-O-sulfite might be predicted to have potency as an HIV-1 Protease inhibitor. Molecular dynamics simulation showed Root Mean Square Fluctuation (RMSF) value of Nigellidine 4-O-sulfite with the amino acid active site is 0.4064 Å for ASP:25 and 0.5667 Å for ASP: 125. Whereas RMSF ligand native with the amino acid active site, ASP: 25 is 0.3647 Å and ASP: 125 is 0.3639 Å. The higher RMSF value of Nigellidine 4-O-sulfite describes the lower interaction stability than the ligand native.

In silico screening of natural products targeting chorismate synthase

Introduction: Chorismate synthase catalyzes the final step in shikimate acid pathway involved in synthesis of aromatic compounds in bacteria.This enzyme can be a possible molecular target for design of antibiotics. Materials and Methods: Homology modeling and molecular dockingwere performed to screen about one hundred natural compounds in order to find inhibitors of enzymes as a possible new target. A model wasbuilt by SWISS-MODEL and its quality was assessed by ERRAT, ProSA, Rampage and MolProbity servers. Docking experiments were performedand pharmacokinetics and toxicities were studied by admetSAR. Results: The predicted model was reliable to be used in docking experiments.Amentoflavone had the highest binding affinity of -10.0 Kcal/mol. Probabilities indicated that rotenone may inhibit P-glycoprotein I, hinokiflavone and silybin may inhibit P-glycoprotein II, while taspine acts on both types of P-glycoproteins. Amentofalavone, hinokiflavone, rotenone and silybin have a probability of inhibiting cytochromes that are involved in oxidation stage of metabolism. Conclusions: These compounds had binding affinities towards FMN binding site of the enzyme model and may be considered in the research for new antibacterial agents but only when their drug interactions are fully investigated.

How feasible is the reversible S-dissociation mechanism for the activation of FeMo-co, the catalytic site of nitrogenase?

Computations with a large enzyme model describe the coordination chemistry and protein involvement that could support the proposed dissociation of S2B from FeMo-co as part of the mechanism of nitrogenase.