IN THE SEARCH OF LEPTIN AGONISTS AS ANTI-OBESITY DRUGS: PROTEIN/PROTEIN DOCKING, MOLECULAR DYNAMICS, AND VIRTUAL SCREENING

The body weight control is a mechanism thinly regulated by several hormonal, metabolic, and nervous pathways (1). Recessive homozygous mutations in the ob/ob and db/db mouse strain cause extreme obesity. The products of the ob and db genes are leptin and its receptor, respectively. The leptin receptor is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased e…