Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2013;8(3):e58774. doi: 10.1371/journal.pone.0058774. Epub 2013 Mar 25.

Computational study of synthetic agonist ligands of ionotropic glutamate receptors.

Author information

1
Department of Theoretical Chemical Biology, Institute for Physical Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany.

Abstract

Neurological glutamate receptors are among the most important and intensely studied protein ligand binding systems in humans. They are crucial for the functioning of the central nervous system and involved in a variety of pathologies. Apart from the neurotransmitter glutamate, several artificial, agonistic and antagonistic ligands are known. Of particular interest here are novel photoswitchable agonists that would open the field of optogenetics to glutamate receptors. The receptor proteins are complex, membrane-bound multidomain oligomers that undergo large scale functional conformational changes, making detailed studies of their atomic structure challenging. Therefore, a thorough understanding of the microscopic details of ligand binding and receptor activation remains elusive in many cases. This topic has been successfully addressed by theoretical studies in the past and in this paper, we present extensive molecular dynamics simulation and free energy calculation results on the binding of AMPA and an AMPA derivative, which is the basis for designing light-sensitive ligands. We provide a two-step model for ligand binding domain activation and predict binding free energies for novel compounds in good agreement to experimental observations.

PMID:
23536824
PMCID:
PMC3607592
DOI:
10.1371/journal.pone.0058774
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center