Philip S. Portoghese, Principal Investigator
and Maria Germana Paterlini, Co-Principal Investigator

Modeling of Opioid and Chemokine Receptors with Their Ligands

  The transmembrane region of opioid receptors was reconstructed based on a previous structural template and recent experimental data on rhodopsin. The intracellular and extracellular loop regions were also modeled by these researchers. These regions, ranging from 0.9 to 25 amino acid residues in length, were studied using a previously developed conformational search algorithm for loops, together with indirect sturctural information obtained through site-directed mutagenesis data, secondary structure prediction and homology modeling. The models were then used to study the binding mode of both endogenous opioid peptides and alkaloids and to suggest possible mechanisms of receptor activation. Following this, the modeling effort was extended to structural models of chemokine receptors implicated in HIV infection. These receptors are homologous to opioid receptors and can be modeled based on sequence homology and available experimental data. Modeling results were used to propose a possible mode of interaction between these receptors and chemokine opioid ligands.