We employed a structural bioinformatics approach to develop novel peptides with predicted affinity to the binding site for negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5). Primary screening in zebrafish () revealed a stimulatory effect of two peptides, LCGM-10 and LCGM-15. Target validation studies using calcium ion flux imaging and a luciferase reporter assay confirmed mGluR5 as the target.
View Article and Find Full Text PDFSoybean is a leguminous plant cultivated in many countries and is considered important in the food industry due to the high levels of oil and protein content in the beans. The high demand for soybeans and its products in the industry requires the expansion of cultivation areas. Despite climatic restrictions, West Siberia is gradually expanding its area of soybean cultivation.
View Article and Find Full Text PDFNegative heterosis can occur on different economically important traits, but the exact biological mechanisms of this phenomenon are still unknown. The present study focuses on determining the genetic factors associated with negative heterosis in interspecific hybrids between domestic sheep () and argali (). One locus (rs417431015) associated with viability and two loci (rs413302370, rs402808951) associated with meat productivity were identified.
View Article and Find Full Text PDFThe aim of the study was to develop better anxiolytics and antidepressants. We focused on GABA receptors and the α2δ auxiliary subunit of V-gated Ca channels as putative targets because they are established as mediators of efficacious anxiolytics, antidepressants, and anticonvulsants. We further focused on short peptides as candidate ligands because of their high safety and tolerability profiles.
View Article and Find Full Text PDFDespite their economic value, sheep remain relatively poorly studied animals in terms of the number of known loci and genes associated with commercially important traits. This gap in our knowledge can be filled in by performing new genome-wide association studies (GWAS) or by re-analyzing previously documented data using novel powerful statistical methods. This study is focused on the search for new loci associated with meat productivity and carcass traits in sheep.
View Article and Find Full Text PDFThe N-glycosylation of immunoglobulin G (IgG) affects its structure and function. It has been demonstrated that IgG N-glycosylation patterns are inherited as complex quantitative traits. Genome-wide association studies identified loci harboring genes encoding enzymes directly involved in protein glycosylation as well as loci likely to be involved in regulation of glycosylation biochemical pathways.
View Article and Find Full Text PDFQuantum mechanics/molecular mechanics (QM/MM) maturation of an immunoglobulin (Ig) powered by supercomputation delivers novel functionality to this catalytic template and facilitates artificial evolution of biocatalysts. We here employ density functional theory-based (DFT-b) tight binding and funnel metadynamics to advance our earlier QM/MM maturation of A17 Ig-paraoxonase (WTIgP) as a reactibody for organophosphorus toxins. It enables regulation of biocatalytic activity for tyrosine nucleophilic attack on phosphorus.
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