Homology modeling, molecular dynamic simulation, and docking based binding site analysis of human dopamine (D4) receptor
- Resource Type
- Authors
- Hamid Nadri; Alireza Moradi; Minasadat Khoddami; Amirhossein Sakhteman
- Source
- Journal of Molecular Modeling. 21
- Subject
- Quantitative structure–activity relationship
Stereochemistry
Molecular Sequence Data
Quantitative Structure-Activity Relationship
Computational biology
Molecular Dynamics Simulation
Biology
Ligands
Molecular Docking Simulation
Catalysis
Inorganic Chemistry
Molecular dynamics
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Homology modeling
Physical and Theoretical Chemistry
Binding site
Root-mean-square deviation
G protein-coupled receptor
Binding Sites
Sequence Homology, Amino Acid
Receptors, Dopamine D4
Organic Chemistry
Computer Science Applications
ROC Curve
Computational Theory and Mathematics
Docking (molecular)
Protein Binding
- Language
- ISSN
- 0948-5023
1610-2940
Human dopamine D4 receptor is a GPCR target in the treatment of neurological and psychiatric conditions such as schizophrenia and Parkinson's disease. The X-ray structure of this receptor has not been resolved so far. Therefore, a proper 3D structure of D4 could provide a good tool in order to design novel ligands against this target. In this study, homology modeling studies were performed to obtain a reasonable structure of the receptor using known templates. The obtained model was subjected to molecular dynamic simulation within a DPPC membrane system. Some structural features of the receptor such as a conserved disulfide bridge and ionic lock were considered in the modeling experiments. The resulted trajectories of simulation were clustered based on the root mean square deviation of the backbone. Some known ligands and decoys were accordingly docked into the representative frames of each cluster. The best final model was finally selected based on its ability to discriminate between active ligands and inactive decoys (ROC = 0.839). The presented model of human D4 receptor could be a promising starting point in future studies of drug design for the described target.