Journal article

Comparing Nonbonded Metal Ion Models in the Divalent Cation Binding Protein PsaA

Hugo MacDermott-Opeskin, Christopher A McDevitt, Megan L O'Mara

Journal of Chemical Theory and Computation | AMER CHEMICAL SOC | Published : 2020


Divalent metal cations are essential for many biological processes; however, accurately modeling divalent metal ions has proved a significant challenge for molecular dynamics force fields. Here we show that the choice of ion model influences the observed dynamics in PsaA, a metal binding protein from Streptococcus pneumoniae. We conduct extensive unbiased simulations and free energy calculations of PsaA bound to its cognate ligand Mn2+ and inhibitory ligand Zn2+ using three nonbonded ion models: a 12-6 model, a 12-6-4 model, and a multisite model. The observed coordination geometries and metal binding dynamics are sensitive to the choice of ion model, with the most dramatic differences obser..

View full abstract


Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council Project Grant (APP1140554). C.A.M. is an Australian Research Council Future Fellow (FT170100006).