caa a22 4500 605513589 CHVBK 20210128100701.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00894-015-2579-3 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2579-3 Homology modeling, molecular dynamic simulation, and docking based binding site analysis of human dopamine (D4) receptor [Elektronische Daten] [Minasadat Khoddami, Hamid Nadri, Alireza Moradi, Amirhossein Sakhteman] 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. Graphical Abstract Superposition of human D4 model with the crystal structure of D3 at TM regions Springer-Verlag Berlin Heidelberg, 2015 Binding site nationallicence Docking nationallicence Homology modeling nationallicence Human dopamine D4 receptor nationallicence Molecular dynamic simulation nationallicence Khoddami Minasadat Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut Nadri Hamid Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut Moradi Alireza Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut Sakhteman Amirhossein Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/2(2015-02-01), 1-10 1610-2940 21:2<1 2015 21 894 https://doi.org/10.1007/s00894-015-2579-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2579-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Khoddami Minasadat Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut NATIONALLICENCE 700 1- Nadri Hamid Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut NATIONALLICENCE 700 1- Moradi Alireza Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran aut NATIONALLICENCE 700 1- Sakhteman Amirhossein Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/2(2015-02-01), 1-10 1610-2940 21:2<1 2015 21 894