Survivin plays a crucial role in cell division particularly during the development of the fetus, in the onset and progression of most tumors and is found expressed in a few terminally differentiated cells. Altogether, there are ten splice variants of survivin, some of which are not yet satisfactorily characterized. Several isoforms may undergo homo/heterodimerization, particularly with the wild-type survivin to elicit a variety of biological functions. The detection of survivin and its splice variants not only suggests the onset, maintenance, and progression of cancer, but also the stage of certain cancers. Recent studies demonstrate that the presence of survivin in urine and blood samples of patients may suggest urogenital and bladder cancer hematologic malignancies, respectively. The expression of the survivin-3α splice variant is indicative of the onset and progression of breast cancer. Several companies have developed cancer diagnostic kits using survivin for detection of cancer. Some are also engaged in fine-tuning the type and stage-specific diagnosis of cancer based on survivin, its splice variants with and without other markers, such as hyaluronidase. Briefly, survivin and its splice variants hold a great biological significance, particularly in the diagnosis of cancer.
a b s t r a c tMammalian gastric lipases are stable and active under acidic conditions and also in the duodenal lumen. There has been considerable interest in acid stable lipases owing to their potential application in the treatment of pancreatic exocrine insufficiency. In order to gain insights into the domain movements of these enzymes, molecular dynamics simulations of human gastric lipase was performed at an acidic pH and under neutral conditions. For comparative studies, simulation of dog gastric lipase was also performed at an acidic pH. Analyses show, that in addition to the lid region, there is another region of high mobility in these lipases. The potential role of this novel region is discussed.
Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.
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