Correlation Engine 2.0
Clear Search sequence regions

Ionotropic glutamate receptors are ligand-gated transmembrane ion channels activated by the binding of glutamate. The free energy landscapes governing the opening/closing of the GluR2 S1S2 ligand-binding domain in the apo, DNQX-, and glutamate-bound forms are computed by using all-atom molecular dynamics simulations with explicit solvent, in conjunction with an umbrella sampling strategy. The apo S1S2 easily accesses low-energy conformations that are more open than observed in X-ray crystal structures. A free energy of 9-12 kcal/mol becomes available upon glutamate binding for driving conformational changes in S1S2 associated with receptor activation. Small-angle X-ray scattering profiles calculated from computed ensemble averages agree better with experimental results than profiles calculated from static X-ray crystal structures. Water molecules in the cleft may contribute to stabilizing the apo S1S2 in open conformations. Free energy landscapes were also computed for the glutamate-bound T686A and T686S S1S2 mutants, and the results elaborate on findings from experimental functional studies.


Albert Y Lau, Benoît Roux. The free energy landscapes governing conformational changes in a glutamate receptor ligand-binding domain. Structure (London, England : 1993). 2007 Oct;15(10):1203-14

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 17937910

View Full Text