Molecular Docking of Opiates and Opioid Peptides, a Tool for the Design of Selective Agonists and Antagonists, and for the Investigation of Atypical Ligand-Receptor Interactions

Abstract

In the last years, molecular docking emerged as a powerful tool to investigate the interactions between opioid ligands and their receptors, thus driving the design and development of new selective agonists or antagonists of therapeutic interest. This review especially covers the most representative and recent comparative molecular docking analyses of structurally related compounds, as well as of agonists and antagonists within the active and inactive states of the receptors. The comparative analyses gave important information on the structural determinants responsible for the affinity and selectivity of the ligands, and defined the features responsible for the activation of the receptors. A special section is dedicated to the analyses of recently discovered, unusual agonists lacking of the tyramine pharmacophore, such as Salvinorin A, and the cyclopeptides which comprise the D-Trp-Phe pharmacophoric motif. For the atypical structure of these compounds, the docking proved to be essential to disclose how they interact with and activate the receptors.

Redoubling the ring size of an endomorphin‐2 analog transforms a centrally acting mu‐opioid receptor agonist into a pure peripheral analgesic

“…It seems that the binding pocket of the mu opioid receptor can accommodate a variety of ligands greatly varying in size. On the other hand, the binding site of kappa is known to be much smaller with respect to mu, so it is likely that a large part of the dimer 2 remains external to the binding pocket but the ligand is still able to bind the kappa with relatively high affinity …”

Characterization of ACE Inhibitory Peptides from Mactra veneriformis Hydrolysate by Nano-Liquid Chromatography Electrospray Ionization Mass Spectrometry (Nano-LC-ESI-MS) and Molecular Docking

“…Molecular docking has been applied to study the structure-activity relationship between bioactive peptides and ACE [7,21]. Previous studies indicate that ACE-binding is strongly influenced by the C -terminal sequence of the peptide; and hydrophobic amino acids at the C -terminus such as Leu, Pro, Phe, Trp, and Tyr, would significantly increase ACE-binding affinity.…”

Naproxen intercalates with DNA and causes photocleavage through ROS generation

“…Molecular docking is a useful tool for obtaining information about the structural features of ligand–receptor complexes and the binding affinity of a ligand with its receptor . Docking studies were therefore performed in an attempt to ascertain the type and amount of interaction between a double‐stranded DNA dodecamer [d(CGCGAATTCGCG) 2 , PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1BNA] and naproxen.…”