Exploring the Structure of Opioid Receptors with Homology Modeling based on Single and Multiple Templates and Subsequent Docking: A Comparative Study
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Exploring the Structure of Opioid Receptors with Homology
Modeling based on Single and Multiple Templates
and Subsequent Docking: A Comparative Study
|
|
| Creator |
Bera, Indrani
Laskar, Aparna Ghoshal, Nanda |
|
| Subject |
Structural Biology & Bioinformatics
|
|
| Description |
Opioid receptors are the principal targets for
opioids, which have been used as analgesics for centuries.
Opioid receptors belong to the rhodopsin family of
G-protein coupled receptors (GPCRs). In the absence of
crystal structures of opioid receptors, 3D homology models
have been reported with bovine rhodopsin as a template,
though the sequence homology is low. Recently, it has been
reported that use of multiple templates results in a better
model for a target having low sequence identity with a
single template. With the objective of carrying out a
comparative study on the structural quality of the 3D
models based on single and multiple templates, the
homology models for opioid receptors (mu, delta and
kappa) were generated using bovine rhodopsin as single
template and the recently deposited crystal structures of
squid rhodopsin, turkey β-1 and human β-2 adrenoreceptors
along with bovine rhodopsin as multiple templates. In
this paper we report the results of comparison between the
refined 3D models based on multiple sequence alignment
(MSA) and models built with bovine rhodopsin as template,
using validation programs PROCHECK, PROSA, Verify
3D, Molprobity and docking studies. The results indicate
that homology models of mu and kappa with multiple
templates are better than those built with only bovine
rhodopsin as template, whereas, in many aspects, the
homology model of delta opioid receptor with single
template is better with respect to the model based on multiple templates. Three nonselective ligands were docked to both the
models of mu, delta and kappa opioid receptors using GOLD
3.1. The results of docking complied well with the pharamacophore,
reported for nonspecific opioid ligands. The comparison
of docking results for models with multiple templates
and those with single template have been discussed in detail.
Three selective ligands for each receptor were also docked. As
the crystallographic structures are not yet known, this
comparison will help in choosing better homology models
of opioid receptors for studying ligand receptor interactions to
design new potent opioid antagonists.
|
|
| Date |
2011
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/104/1/JOURNAL_OF_MOLECULAR_MODELING%2C_17(_5)1207%2D1221%2C2011_[53].pdf
Bera, Indrani and Laskar, Aparna and Ghoshal, Nanda (2011) Exploring the Structure of Opioid Receptors with Homology Modeling based on Single and Multiple Templates and Subsequent Docking: A Comparative Study. Journal of Molecular Modeling, 15 (7). pp. 1207-1221. |
|
| Relation |
http://dx.doi.org/10.1007/s00894-010-0803-8
http://www.eprints.iicb.res.in/104/ |
|