Structure-Based virtual screening for novel modulators of human Orexin 2 receptor with cloud systems and supercomputers

Abstract

Narcolepsy is a chronic neurologic disease characterized by excessive and inappropriate daytime sleepiness. Its pathophysiology is closely associated with the neuropeptide orexin, the absence of which is now believed to be responsible for most of the symptoms of the disease. Currently, no therapeutics against narcolepsy are available and afflicted patients are treated only symptomatically. Therefore, development of small-molecules able to penetrate into the brain and activate the orexin receptors represents a hopeful way. In this work we describe a computational approach which applies structure-based virtual screening of 1 million ligands to find novel potential modulators of orexin 2 receptor (OX2R). So-called rational computer-aided search for OX2R modulators was performed on a software-asa-service (SaaS) cloud platform using iDock molecular docking program as a virtual screening engine. The results of the cloud-based calculations with iDock are analyzed and compared with the results of high-throughput flexible molecular docking in AutoDock Vina employing a pleasingly parallelized computation scheme on a peta-flops-scale supercomputer.