Predictions of binding for dopamine D2 receptor antagonists by the SIE method.
The control of tetralindiol derivative antagonists released through the inhibition of dopamine D2 receptors has been identified as a potential target for the treatment of schizophrenia. We employed molecular dynamics simulation techniques to identify the predicted D2 receptor structure. Homology models of the protein were developed on the basis of crystal structures of four receptor crystals. Compound docking revealed the possible binding mode. In addition, the docking analyses results indicate that five residues (Asp72, Val73, Cys76, Leu183, and Phe187) were responsible for the selectivity of the tetralindiol derivatives. Our molecular dynamics simulations were applied in combination with the solvated interaction energies (SIE) technique to predict the compounds' docking modes in the binding pocket of the D2 receptor. The simulations revealed satisfactory correlations between the calculated and experimental binding affinities of all seven tetralindiol derivative antagonists, as indicated by the obtained R2 value of 0.815.
Wang
Yeng-Tseng
YT
National Center for High-performance Computing, Hsin-Shi, Tainan County 741, Taiwan. c00jsw00@nchc.org.tw
Su
Zhi-Yuan
ZY
Hsieh
Chang-Huain
CH
Chen
Cheng-Lung
CL
D000595:Amino Acid Sequence; D065127:Dopamine D2 Receptor Antagonists; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
D065127:Dopamine D2 Receptor Antagonists; D006571:Heterocyclic Compounds; D017448:Receptors, Dopamine D2; D012997:Solvents