Dissertation > Excellent graduate degree dissertation topics show

Homology Modeling and Molecular Docking Simulation on Dopamine D1-Like Receptor

Author: LiKui
Tutor: LiYanNi
School: Tianjin University
Course: Pharmaceutical Engineering
Keywords: Dopamine dopamine D1-like receptor homology modeling molecular docking
CLC: Q51
Type: Master's thesis
Year: 2009
Downloads: 55
Quote: 1
Read: Download Dissertation

Abstract

Homology modeling and molecular docking simulation are used to study the human dopamine D1-like receptor in this article. The main purpose is to build the D1 and D5 receptor’s three-dimensional models at the molecular level, and then use the two models and some ligands for docking simulation study. Through analysis of the interacting modes between the ligands and the dopamine receptors, to clarify their interacting mechanism and explain activity differences among three antagonist analogies interacting with dopamine receptor.Homology modeling indicates that: it is reasonable to use adrenergic receptor 2vt4 crystal structure as template to build D1 and D5 dopamine receptor’s three-dimensional models. When these models are built they are further optimized and molecular dynamic simulation is performed, and then PROCHECK, ERRAT and PROSA programs are used for energy and conformation evaluation and dopamine is used for molecular docking. The final results substantiate the accuracy of models.Antagonist SCH23390 and agonist SKF38393 molecular docking simulation study shows that: when antagonist SCH23390 interacts with D1 and D5 receptors, they form two pairs of hydrogen bonding and have a strong hydrophobic interaction. It forms strong electrostatic interaction with D1 receptor, but weak with D5 receptor. D5 receptor binding site is more exposed, and has several binding sites. Docking with the antagonist SCH23390, two same residues of the two receptors that involve in the formation of hydrogen bonds respectively prove their importance and conservative. As for the interactions between agonist SKF38393 and D1, D5 receptor respectively, the electrostatic and hydrogen bonding interactions are strong, but hydrophobic interaction is very weak.Finally, activity discrepances of the three antagonist analogues are elaborated theoretically based on molecular docking of the three antagonist analogues and analysis of the hydrogen bonding, hydrophobic and electrostatic interactions between them and D1 and D5 receptors respectively.

Homology Modeling and Molecular Docking Simulation on Dopamine D1-Like Receptor

Abstract

Related Dissertations