Computer-Aided Drug Design Against Dopamine D2 Receptor …
105
Table 3 AutoDock Vina result for all compounds
Compound
RMSD Affinity score with respect to lower RMSD
(kcal/mol)
ETICLOPRIDE
1.15
−7.4
C16H24ClN3O3 (36th compound)
0.277
−8
C16H21ClF2N2O3 (96th compound) 0.699
−8.7
RMSD Root mean square division
Table 4 iGEM Docking result for total energy Eticlopride and other two newly derived lead
compounds
Compound
Total energy (kJ/mol)
C16H24ClN3O3 (36th compound)
−98.46
C16H21ClF2N2O3 (96th compound)
−92.32
Eticlopride
−82.93
3.2 Docking (AutoDock Vina and IGEM)
According to AutoDock Vina, the affinity score is equivalent to the ΔG value. So
lower the ΔG value and lower RMSD values are the two key factors to determine the
binding efficiency of lead compounds towards receptor. From AutoDock Vina result,
the RMSD values are estimated on energy involved in protein-ligand interaction.
Difference between two RMSDs (ub-lb) was taken as indication of best pose with
respect to high affinity for comparison between modified leads and Eticlopride with
respect to Dopamine D2 receptor. For 36th and 96th compound, the RMSD values
were found to be 0.277 and 0.699, respectively, which are lower in comparison to
Eticlopride whose RMSD found to be 1.15. This can be stated hypothetically that
new compounds are more capable to form stable complex with dopamine d2 than
that of eticlopride (Tables 3 and 4).
iGEMDOCK ranks all the screening compounds based on the energy involved
and pharmacological scoring function and clusters the compounds on the basis of
their chemical composition. According iGEMDOCK standard report 36th compound
has ranked first with total energy l, 96th compound as second with total energy and
Eticlopride as third with total energy which implies that both of the new compounds
have higher efficiency to bind with D2R.
3.3 Docking (Cluspro)
After doing docking between NCS1 (wild type) and D2R in CLUSPRO docking tool,
the hotspot of NCS1 has been found to be PHE55, LEU189 and GLU142 with help
of PPCHECK web server (Table 5).
105
Table 3 AutoDock Vina result for all compounds
Compound
RMSD Affinity score with respect to lower RMSD
(kcal/mol)
ETICLOPRIDE
1.15
−7.4
C16H24ClN3O3 (36th compound)
0.277
−8
C16H21ClF2N2O3 (96th compound) 0.699
−8.7
RMSD Root mean square division
Table 4 iGEM Docking result for total energy Eticlopride and other two newly derived lead
compounds
Compound
Total energy (kJ/mol)
C16H24ClN3O3 (36th compound)
−98.46
C16H21ClF2N2O3 (96th compound)
−92.32
Eticlopride
−82.93
3.2 Docking (AutoDock Vina and IGEM)
According to AutoDock Vina, the affinity score is equivalent to the ΔG value. So
lower the ΔG value and lower RMSD values are the two key factors to determine the
binding efficiency of lead compounds towards receptor. From AutoDock Vina result,
the RMSD values are estimated on energy involved in protein-ligand interaction.
Difference between two RMSDs (ub-lb) was taken as indication of best pose with
respect to high affinity for comparison between modified leads and Eticlopride with
respect to Dopamine D2 receptor. For 36th and 96th compound, the RMSD values
were found to be 0.277 and 0.699, respectively, which are lower in comparison to
Eticlopride whose RMSD found to be 1.15. This can be stated hypothetically that
new compounds are more capable to form stable complex with dopamine d2 than
that of eticlopride (Tables 3 and 4).
iGEMDOCK ranks all the screening compounds based on the energy involved
and pharmacological scoring function and clusters the compounds on the basis of
their chemical composition. According iGEMDOCK standard report 36th compound
has ranked first with total energy l, 96th compound as second with total energy and
Eticlopride as third with total energy which implies that both of the new compounds
have higher efficiency to bind with D2R.
3.3 Docking (Cluspro)
After doing docking between NCS1 (wild type) and D2R in CLUSPRO docking tool,
the hotspot of NCS1 has been found to be PHE55, LEU189 and GLU142 with help
of PPCHECK web server (Table 5).