In order to address these issues, we constructed structural models of lurasidone GPCR complexes by homology modeling of receptors, exhaustive docking of ligand, and molecular dynamics simulation-based refinement of complexes.
computing synaptic conductances based on a kinetic model of receptor binding.
This study reveals a diffusion-and-capture mechanism to organize low copy number membrane-anchored receptors dependent on the DNA, while other models of receptor localization are excluded experimentally.
Different studies have presented a multistate model of receptor activation in which ligand-specific receptor conformations are able to differentiate between distinct signalling partners.
We find that the fluorescence resonance energy transfer results for wild-type and for a low-activity mutant are inconsistent with the lattice models of receptor coupling, but consistent with the Monod-Wyman-Changeux model of receptor coupling, suggesting that receptors form isolated strongly-coupled clusters.
According to the traditional two-state model of receptor theory, GPCRs were considered as operating in equilibrium between two functional conformations, an active (R*) and inactive (R) state.
We compare in detail the activity response of coupled two-state receptors for different models of receptor coupling: weakly-coupled extended one-dimensional and two-dimensional lattice models and the Monod-Wyman-Changeux model of isolated strongly-coupled clusters.
We discuss the implications of these findings for current models of receptor assembly and diversification.
The new findings suggest an expansion of the classical ternary complex model of receptor action to include an explicit isomerization of the receptors from an inactive to an active state which couples to the G protein ('allosteric ternary complex model').
