Comparison of dopamine D2 receptor (homology model and X-ray structure) and virtual screening protocol validation for the antagonism mechanism

ABSTRACT

The present research work aims to compare the homology model and recent X-ray crystal structure of dopamineD2 receptor (PDB Code 6CM4) as well as to validate the virtual screening protocol for antagonist compounds. Thecomparison involved the sequence similarity and the capability of both proteins to produce similar risperidone bindingpose with co-crystal structure based on ChemPLP score and Tanimoto Coefficient score generated by PLANTS andPyplif. Homology model failed to give the correct binding pose as the root mean square deviation fell to >2Å evenwith similar sequence and folding. Therefore, 6CM4 should be used for virtual screening instead of the homologymodel. The virtual screening protocol validation of 6CM4 was performed by PLANTS followed by Pyplif filtering.The protocol was able to give EF1% value of 6.238, which was better than the EF1% value of protein dopamine D3receptor that shared >80% similarity with dopamine D2 receptor. Similarity between the docking pose and the actualpose is considered important to obtain better predictivity