Periodic force induced stabilization or destabilization of the denatured state of a protein

We have studied the effects of an external sinusoidal force in protein folding kinetics. The externally applied force field acts on the each amino acid residues of polypeptide chains. Our simulation results show that mean protein folding time first increases with driving frequency and then decreases passing through a maximum. With further increase of the driving frequency the mean folding time starts increasing as the noise-induced hoping event (from the denatured state to the native state) begins to experience many oscillations over the mean barrier crossing time period. Thus unlike one-dimensional barrier crossing problems, the external oscillating force field induces both \emph{stabilization or destabilization of the denatured state} of a protein. We have also studied the parametric dependence of the folding dynamics on temperature, viscosity, non-Markovian character of bath in presence of the external field

Systematic elucidation of the traditional Chinese medicine prescription Danxiong particles via network pharmacology and molecular docking

Purpose: To investigate the pharmacological effect of the traditional Chinese medicine (TCM) prescription Danxiong particles (TDX105) and its mechanism of action.Methods: The active compound and targets of TDX105 were investigated via network pharmacology. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched, and protein-protein interaction network (PPI) was constructed. A network of ‘components-targets-pathways’ was developed with Cytoscape 3.8.0 software, while the formation of molecular docking analysis was conducted using Autodock vina software.Results: There were 304 compounds and 482 targets identified in total. Genes with degree ≥ mean node values were selected as the crucial targets, and string database was to be combined to 64 targets identified with cytoscape so as to draw a protein interaction map. A total of 137 pathways were enriched from 64 targets involving mainly 10 pathways, for example, PI3K-Akt signaling pathway, pathways in cancer, human cytomegalovirus infection and focal adhesion. Then, compound-target and compoundtarget- pathways were constructed using cytoscape (3.8.0). Finally, the five most active compounds, viz, quercetin, myricetin, luteolin, ellagic acid and kaempferol, and the top ten targets AKT1, GAPDH, TP53, ALB, EGFR, MAPK3, JUN, MAPK1, SRC and ESR1 were selected for molecular docking. These targets and compounds had strong interactions through a combination of hydrogen bonds and hydrophobic forces.Conclusion: The mechanism of action of TDX105 has been successfully explained using the combination of network pharmacology and molecular docking. This may offer a solid foundation to the clinical use of TDX105, and further strengthen the prospects of its development for clinical use