Computer-Aided Drug Design Against Dopamine D2 Receptor …
103
Table 1 Mutations introduced in NCS1 (Neuronal calcium sensor-1)
Control NCS1
Mutated towards hydrophilic
Mutated towards hydrophobic
PHE 55
ARG 55
ILE 55
LEU 189
ARG 189
ILE 189
PHE Phenylalanine, LEU Leucine, ARG Arginine, ILE Isoleucine
compounds. Compounds with better ADMET values than that of Eticlopride were
docked with Dopamine D2 receptor for estimating binding efficacy.
2.2 Docking with AutoDock Vina and IGEM Docking
For molecular docking AutoDock Vina uses a hybrid scoring function of empirical
and knowledge-based functions in calculation of X-Score to determine the best poses.
iGEMDOCK, on the other hand, uses energy-based scoring function that is composed
of electrostatic, hydrogen bonding and Van der Waals interaction between protein
and ligand molecules. Henceforth in this research work both docking tools have been
utilized for cross-validation of the binding affinity of newly derived leads towards
D2R.
2.3 Introduction of Mutation in Ncs1 Docking
Docking has been performed between wild type NCS1 (Phyre2 id d1g8ia) and D2R
(PDBID 6CM4). Posts docking the binding hotspot and total stabilizing energy have
been analyzed with the help of PPCHECK. Hydrophobic amino acid residues present
in the HOTSPOT have been mutated to introduce hydrophilic and more hydrophobic
amino acids with the SWISSPDB VIEWER and the structural stability estimated.
Docking has been done with the help of CLUSTER PRO DOCKING tool between
mutated NCS1 and D2R. G, Kd values and total stabilizing energy values were
determined with the help of computational tools like PP CHECK and PRODIGY
(Table 1).
3 Result and Discussion
3.1 Physicochemical Property
From ADMET lab report, the hepatotoxicity probability of compound 36th
(C16H24ClN3O3) and compound 96th (C16H21ClF2N2O3) are 0.66 and 0.62,
103
Table 1 Mutations introduced in NCS1 (Neuronal calcium sensor-1)
Control NCS1
Mutated towards hydrophilic
Mutated towards hydrophobic
PHE 55
ARG 55
ILE 55
LEU 189
ARG 189
ILE 189
PHE Phenylalanine, LEU Leucine, ARG Arginine, ILE Isoleucine
compounds. Compounds with better ADMET values than that of Eticlopride were
docked with Dopamine D2 receptor for estimating binding efficacy.
2.2 Docking with AutoDock Vina and IGEM Docking
For molecular docking AutoDock Vina uses a hybrid scoring function of empirical
and knowledge-based functions in calculation of X-Score to determine the best poses.
iGEMDOCK, on the other hand, uses energy-based scoring function that is composed
of electrostatic, hydrogen bonding and Van der Waals interaction between protein
and ligand molecules. Henceforth in this research work both docking tools have been
utilized for cross-validation of the binding affinity of newly derived leads towards
D2R.
2.3 Introduction of Mutation in Ncs1 Docking
Docking has been performed between wild type NCS1 (Phyre2 id d1g8ia) and D2R
(PDBID 6CM4). Posts docking the binding hotspot and total stabilizing energy have
been analyzed with the help of PPCHECK. Hydrophobic amino acid residues present
in the HOTSPOT have been mutated to introduce hydrophilic and more hydrophobic
amino acids with the SWISSPDB VIEWER and the structural stability estimated.
Docking has been done with the help of CLUSTER PRO DOCKING tool between
mutated NCS1 and D2R. G, Kd values and total stabilizing energy values were
determined with the help of computational tools like PP CHECK and PRODIGY
(Table 1).
3 Result and Discussion
3.1 Physicochemical Property
From ADMET lab report, the hepatotoxicity probability of compound 36th
(C16H24ClN3O3) and compound 96th (C16H21ClF2N2O3) are 0.66 and 0.62,