Molecular Basis of Partial Agonism at the 5HT2A receptor: orientation of indolamines in the binding pocket determines relative efficacy.
Barbara J. Ebersole, Irache Visiers, Daqun Zhang, Harel Weinstein, Stuart Sealfon

The following movies are available.

1. 5HT in the binding site of the WT receptor:
The initial placement of 5HT in the binding site is such that 5HT hydrogen bonds residues D3.32 and S3.36.

2. 5HT and 1-N,N-dMe-5HT in the WT receptor: The orientation adopted by 5HT and 1-N,N-dMe-5HT in the WT after the molecular dynamics simulation is quite diferent. During the simulation N,N-dMe-5HT reorganizes in the binding pocket to avoid the steric clash between its methyl substituted side chain and the Ser3.36 hydroxyl group. Note that N,N-dMe-5HT only maintains the hydrogen bond with D3.32 but not with S3.36.

3. 5HT in S3.36A mutant receptor: In the absence of a serine at position 3.36, 5HT loses the hydrogen bond with S3.36 and 5HT moves away from position 3.36 during the molecular dynamics simulation.

4. 5HT and 1-N-Me-5HT in S5.46A mutant receptor: The orientation of 5HT and 1-N-Me-5HT in the S5.46A mutant receptor is nearly overlapping.

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Irache Visiers