Homology Modeling and Molecular Dynamics Simulations of the Glycine Receptor Ligand Binding Domain.
From: Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
Proteins
- Publish Date: Jun 2007
- ISSN: 1097-0134
- Volume: 67
- Issue: 4
- Pages: 950-60
- Medium: Internet
- Language: English
- Citation (JAMA): Speranskiy Kirill, Cascio Michael, Kurnikova Maria, et al. Homology Modeling and Molecular Dynamics Simulations of the Glycine Receptor Ligand Binding Domain.. Proteins Jun 2007;67:950-60
Abstract
We present a homology based model of the ligand binding domain (LBD) of the homopentameric alpha1 glycine receptor (GlyR). The model is based on multiple sequence alignment with other members of the nicotinicoid ligand gated ion channel superfamily and two homologous acetylcholine binding proteins (AChBP) from the freshwater (Lymnaea stagnalis) and saltwater (Aplysia californica) snails with known high resolution structure. Using two template proteins with known structure to model three dimensional structure of a target protein is especially advantageous for sequences with low homology as in the case presented in this paper. The final model was cross-validated by critical evaluation of experimental and published mutagenesis, functional and other biochemical studies. In addition, a complex structure with strychnine antagonist in the putative binding site is proposed based on docking simulation using Autodock program. Molecular dynamics (MD) simulations with simulated annealing protocol are reported on the proposed LBD of GlyR, which is stable in 5 ns simulation in water, as well as for a deformed LBD structure modeled on the corresponding domain determined in low-resolution cryomicroscopy structure of the alpha subunit of the full-length acetylcholine receptor (AChR). Our simulations demonstrate that the beta-sandwich central core of the protein monomer is fairly rigid in the simulations and resistant to deformations in water.
Mesh Headings (Keywords): Amino Acid Sequence, Binding Sites, Computer Simulation, Conserved Sequence, Ligands, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Subunits, Receptors, Glycine, Sequence Alignment, Structural Homology, Protein
Check for Full Text / PubMed Unique Identifier (PMID): 17357155
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.