PMID- 25259728
OWN - NLM
STAT- MEDLINE
DCOM- 20150814
LR  - 20231213
IS  - 1742-2051 (Electronic)
IS  - 1742-2051 (Linking)
VI  - 10
IP  - 12
DP  - 2014 Dec
TI  - The nociceptin receptor (NOPR) and its interaction with clinically important 
      agonist molecules: a membrane molecular dynamics simulation study.
PG  - 3188-98
LID - 10.1039/c4mb00323c [doi]
AB  - The nociceptin receptor (NOPR) is an orphan G protein-coupled receptor that 
      contains seven transmembrane helices. NOPR has a distinct mechanism of 
      activation, though it shares a significant homology with other opioid receptors. 
      Previously there have been reports on homology modeling of NOPR and also 
      molecular dynamics simulation studies for a short period. Recently the crystal 
      structure of NOPR was reported. In this study, we analyzed the time dependent 
      behavior of NOPR docked with clinically important agonist molecules such as NOP 
      (natural agonist) peptide and compound 10 (SCH-221510 derivative) using molecular 
      dynamics simulations (MDS) for 100 ns. Molecular dynamics simulations of 
      NOPR-agonist complexes allowed us to refine the system and to also identify 
      stable structures with better binding modes. Structure activity relationships 
      (SAR) for SCH221510 derivatives were investigated and reasons for the activities 
      of these derivatives were determined. Our molecular dynamics trajectory analysis 
      of NOPR-peptide and NOPR-compound 10 complexes found residues to be crucial for 
      binding. Mutagenesis studies on the residues identified from our analysis could 
      prove useful. Our results could also provide useful information in the 
      structure-based drug design of novel and potent agonists targeting NOPR.
FAU - Kothandan, Gugan
AU  - Kothandan G
AD  - Centre of Advanced Study in Crystallography and Biophysics, University of Madras, 
      Guindy Campus, Chennai-600025, India. gugan@unom.ac.in.
FAU - Gadhe, Changdev G
AU  - Gadhe CG
FAU - Balupuri, Anand
AU  - Balupuri A
FAU - Ganapathy, Jagadeesan
AU  - Ganapathy J
FAU - Cho, Seung Joo
AU  - Cho SJ
LA  - eng
PT  - Journal Article
DEP - 20140926
PL  - England
TA  - Mol Biosyst
JT  - Molecular bioSystems
JID - 101251620
RN  - 0 (8-(bis(2-methylphenyl)methyl)-3-phenyl-8-azabicyclo(3.2.1)octan-3-ol)
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (Opioid Peptides)
RN  - 0 (Receptors, Opioid)
RN  - 0 (Nociceptin Receptor)
SB  - IM
MH  - Animals
MH  - Azabicyclo Compounds/chemistry
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Mice
MH  - Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Opioid Peptides/chemistry
MH  - Protein Conformation
MH  - Receptors, Opioid/*agonists/*chemistry
MH  - Nociceptin Receptor
MH  - Nociceptin
EDAT- 2014/09/27 06:00
MHDA- 2015/08/15 06:00
CRDT- 2014/09/27 06:00
PHST- 2014/09/27 06:00 [entrez]
PHST- 2014/09/27 06:00 [pubmed]
PHST- 2015/08/15 06:00 [medline]
AID - 10.1039/c4mb00323c [doi]
PST - ppublish
SO  - Mol Biosyst. 2014 Dec;10(12):3188-98. doi: 10.1039/c4mb00323c. Epub 2014 Sep 26.