Using Atomistic Simulations to Explore the Role of Methylation and ATP in Chemotaxis Signal Transduction

[Image: see text] A bacterial chemotaxis mechanism is activated when nutrients bind to surface receptors. The sequence of intra- and interprotein events in this signal cascade from the receptors to the eventual molecular motors has been clearly identified. However, the atomistic details remain elusive, as in general may be expected of intraprotein signal transduction pathways, especially when fibrillar proteins are involved. We performed atomistic calculations of the methyl accepting chemoprotein (MCP)–CheA–CheW multidomain complex from Escherichia coli, simulating the methylated and unmethylated conditions in the chemoreceptors and the ATP-bound and apo conditions of the CheA. Our results indicate that these atomistic simulations, especially with one of the two force fields we tried, capture several relevant features of the downstream effects, such as the methylation favoring an intermediate structure that is more toward a dipped state and increases the chance of ATP hydrolysis. The results thus suggest the sensitivity of the model to reflect the nutrient signal response, a nontrivial validation considering the complexity of the system, encouraging even more detailed studies on the thermodynamic quantification of the effects and the identification of the signaling networks.