I spent some time examining the conformation of opioids like Dimethylaminopivalophenone. I don't know if it's just my stupidity but can't this compounds equally conform to 2 different shapes? One of them overlays pethidine, the other does not. Similarly propiram with it's tertiary nitrogen is able to assume 2 different conformations. Do these compounds interconvene with the binding holding it into the active conformation?
I overlaid compounds like propiram with norbutorphanol (a rigid opioid) and it looks like 50% of the time, the aromatic and N: overlay perfectly and 50% of the time, they did not seem to overlay at all.
Maybe it's my stupidity but I did wonder if the weak opioids WERE weak because 50% of the atoms were not in the correct confirmation.
I overlaid compounds like propiram with norbutorphanol (a rigid opioid) and it looks like 50% of the time, the aromatic and N: overlay perfectly and 50% of the time, they did not seem to overlay at all.
Maybe it's my stupidity but I did wonder if the weak opioids WERE weak because 50% of the atoms were not in the correct confirmation.