A Science paper titled “Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions” by the group of Professor R. C. Stevens at The Scripps Research Institute in La Jolla, CA (USA) has confirmed the role of sodium ions in the allosteric regulation of GPCRs as it had been modeled by Selent et al. in 2010 using high-throughput MD simulations on ACEMD.
Results by Stevens Group shed on the importance of endogenous small molecules at specific binding sites as control mechanisms of membrane proteins. Such concept exceeds the common view of allostery via pharmacological ligands. The results have profound effects on the current understanding of the functional mechanisms of GPCRs, a broad family of proteins that comprises many of today’s pharmacological targets.
In that regard, computational modeling of small molecule-protein interactions using ACEMD has proven powerful tool to predict unknown solvent-derived effects on protein function.
– Liu W., et al., Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions, Science 2012: 337 (6091), 232-236. DOI:10.1126/science.1219218
– Selent J., et al., Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors, PLOS Computational Biology 2010, 6, e1000884. DOI:10.1371/journal.pcbi.1000884
– Source: The Scripps Research Institute