Ca2+ and Mg2+ cations play a central role in a number of fundamental biological processes, from calcium signaling to Mg2+-dependent activity of ribozymes and RNA-processing enzymes. Standard biomolecular simulations with divalent cations using non-polarizable force fields suffer from severe overbinding artifacts, in addition to challenging sampling problems.
We develop a scaled charge approach, which takes into account electronic polarization in a mean-field way. We show that it successfully improves ion-binding properties to typical biomolecular groups, and present our current efforts to extend it to polyphosphate species (e.g. ATP) and DNA/RNA. This method thus opens the way to large-scale, accurate, and computationally cheap simulations of divalent cation containing (bio)systems.
We also use molecular simulations to investigate the stability and conformational fluctuations of a rRNA:M5 complex involved in rRNA maturation, where experimental data suggest a 2-ion mechanism. We find that fluctuations of interfacial contacts are correlated with distinct active site conformations, that seem prone to react according to distinct reaction mechanisms. QM/MM-MD dynamic exploration of the reaction free energy landscape is then performed to characterize the mechanisms in each conformation.

Contact: Emmanuelle Bignon