Computational structural biology of opioid receptors

The publication of high-resolution structures for all of the opioid receptor subfamilies has unveiled exciting opportunities for mechanistic insight into the molecular mechanisms underlying the biology of nociception, reward, and higher cognitive functions, as well as promises for progress in several clinical areas such as pain management, physiological dependence, addiction, and mood disorders. To turn this promise into novel and improved therapeutic entities, however, this information needs to be supplemented with research strategies that explore the dynamic behavior of the proteins and their interactions with other receptors and ligands in their physiological environment. Here we describe state-of-the-art molecular dynamics computational protocols, based on all-atom and coarse-grained modeling techniques, designed to estimate crucial thermodynamic and kinetic parameters describing the binding of small-molecule ligands and the formation of supramolecular complexes.