2011 GPCR Structure Ligand Selection Assessment


GPCR Network Center

We have conducted two GPCR modeling/docking assessments over the past 3 years, and for a change of pace, we would like to propose a new type of assessment, namely the selection of what ligand(s) will best stabilize a specific GPCR and lead to crystallization and structure determination.

Our understanding of receptor-ligand stabilization is an important fundamental question for GPCR biology, and we do not have a good understanding of this area. Almost certainly, the characteristics of the ligands will be a combination of affinity, solubility, slow off-rate, etc... With the recent structure determination of the A2a adenosine receptor agonist (UK432097) complex, our thoughts on the type of pharmacological molecule (agonist vs antagonist) are less defined since this molecule had modest solubility and was an agonist, yet it was very stabilizing and led to a structure determination. Since novel thinking in drug discovery is needed, we believe research in the area of receptor-ligand stabilization area may help us discover new insights into GPCR-ligand interactions.

To try and catalyze some creativity in this area, we would like to challenge the computational and opioid research community to predict which ligands will help stabilize the 4 opioid receptors the most (NOP, kappa, delta, mu) and that will lead to the first opioid structure. Whomever selects the successful ligand will be invited to participate in the writing of the paper including authorship pending intellectual contribution in the data analysis and manuscript writing. If you are interested in this, please submit up to 5 ligands per each of the 4 opioid receptors, prioritized in order of top choice first. The ligands should be commercially available (with vendor listed we can order from), or if they are not commercially available, they need to be directly sent to us for the experiments. For the most adventurous, designing a tool compound and getting it synthesized and tried will be the ultimate challenge.

This assessment will be published as a separate study on ligand-receptor interactions. We hope this assessment will catalyze new ideas in the GPCR field.

We encourage all industry and academic groups to participate and so please pass word of this assessment onto your colleagues who may have not directly been contacted.

For questions, please contact [opioids at scripps.edu] and we will try to quickly respond.

If you are interested in participating in this assessment, please register below and then follow the instructions for ligand submission. By accepting the information, you agree that within the best of your ability, you will submit a ligand or ligands for this initiative. All ligands may be submitted until the first opioid structure has been solved.

Please use the following link to submit/deposit your ligands: Ligand Submission.

Please note:
Registration and the assessment are now closed.