To obtain the affinities between drugs and neuroreceptors, the protocol is as follows:
-list neuroreceptors known to play a role in psychoactive effects
-identify potential docking sites on neuroreceptors (based on this work http://www.pkumdl.cn:8000/cavityspace/about )
Perform GNINA binding energy minimization for each pair of drug and docking site ( paper: https://jcheminf.biomedcentral.com/articles/10.1186/s13321-021-00522-2 tool: https://github.com/gnina/gnina )
-Assign an affinity score to each pose with GNINA
Limitations:
-The same neuroreceptor may vary between individuals
-A neuroreceptor is a structure that can have several “modes”, be in different configurations
-Only docking sites (pockets) with the highest probability identified by CavitySpace were retained
-Other molecules may interact between the neuroreceptor and the drug
-GNINA was used with parameters to reduce computation time and therefore accuracy (in particular, a completeness of 8 and the default scoring model)
-A ligand can conform in a pocket in several ways, which are not always of minimal binding energy and impacting the nature of the interaction
Many of these constraints are lack of exhautivity due to the project’s limited material resources