Molecular dynamics simulations of human and dog gastric lipases: insights into domain movements

Mammalian 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.