Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach.

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of -32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.

Sesame oil ameliorates valproic acid-induced hepatotoxicity in mice: integrated in vivo-in silico study.

Sesame oil (SO) has been exhibited to have anti-inflammatory and antioxidant influences. The goal of this experiment was to look into SO's hepato-protective properties and underlying processes in valproic acid (VPA)-induced hepatotoxicity. Molecular docking was carried out to clarify the functional and structural underlying mechanism of SO ameliorative effect. Mice were given 8 mL/kg/day of SO (orally) and 100 mg/kg/day of VPA (i.p.) for 21 days. The results revealed that VPA caused a considerable increase in hepatic malondialdehyde levels while decreasing the activity of glutathione peroxidase (GPx) enzyme. There was also a significant rise in serum levels of interleukins 1ß and 6 (IL-1ß and IL-6) and a significant decrease in hepatic (PXR) gene expression level. SO co-administration with VPA significantly normalized the antioxidant and anti-inflammatory status and upregulated the gene expression level of PXR. In silico docking analysis results confirmed these results. This study concluded that supplementation of SO attenuated VPA-induced oxidative stress and inflammation. Hence, it was recommended as a dietary supplement for protection against VPA-induced hepatotoxicity.Communicated by Ramaswamy H. Sarma.

Inhibition analysis of aflatoxin by in silico targeting the thioesterase domain of polyketide synthase enzyme in Aspergillus ssp.

The spread of fungal growth causes enormous economic, agricultural, and health problems for humans, such as Aspergillus sp., which produce aflatoxins. Thus, the inhibition of aflatoxin production became a precious target. In this research, the thioesterase (TE) domain from Polyketide synthase enzyme was selected to employ the in silico docking, using AutoDock Vina, against 623 natural compounds from the South African natural compound database (SANCDB), to identify potential inhibitors that can selectively inhibit thioesterase domain. The top ten inhibitors components were pinocembrin, typhaphthalide, p-coumaroylputrescine, dilemmaone A, 9-angelylplatynecine, 2,4,6-octatrienal, 4,8-dichloro-3,7-dimethyl-, (2e,4z,6e)-, lilacinobiose, 1,3,7-octatriene, 5,6-dichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(e)]-(-)- (9ci), lilacinobiose, 1,3,7-octatriene, 5,6-dichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(e)]-(-)- (9ci), 1,3,7-octatriene, 1,5,6-trichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(z,e)] and 9-angelylhastanecine and that depending on the lowest binding energy, the best chemical interactions and the best drug-likeness. The results of those components gave successful inhibition with the thioesterase domain. So, they can be used for inhibition and controlling aflatoxin contamination of agriculture crop yields, specially, pinocembrin which gave promising results.Communicated by Ramaswamy H. Sarma.

In silico Targeting, inhibition and analysis of polyketide synthase enzyme in Aspergillus ssp.

Aflatoxins are toxic and carcinogenic components produced by some Aspergillus species such as Aspergillus flavus. Polyketide synthases enzyme (PKS) plays a central role in aflatoxin s biosynthesis of in Aspergillus flavus, especially the product template (PT) domain, which controls the aldol cyclization of the polyketide forerunner during the biosynthesis of the aflatoxin pathway process. Here, we apply the in silico approaches to validate 623 natural components obtained from the South African Natural Compound Database (SANCDB), to distinguish the PT domain s prospected inhibitors. From the 623 compounds, docking results showed that there are 330 different compounds with energy binding lower than the natural substrate (palmitic acid or PLM) of the Product Templet domain (PT). Three factors were selected to determine the best 10 inhibiting components; 1) energy binding, 2) the strengthen chemical interactions, 3) the drug-likeness. The top ten inhibiting components are kraussianone 6, kraussianone 1, neodiospyrin, clionamine D, bromotopsentin, isodiospyrin, spongotine A, kraussianone 3, 14ß-Hydroxybufa-3,5,20,22-tetraenolide and kraussianone 7. The chemical interactions between 3HRQ domain and the natural substrate in the active site amino acids are highly similar to the 3HRQ with the top ten components, but the main differences are in the binding energy which is the best in the top ten ligands. Those ten components give successful inhibition with PT domain which will lead to the formula to be used for inhibition and control aflatoxin contamination of agriculture crop yields and lessen the degree of harming and sicknesses that are coming about because of acquiring measures of aflatoxin.