Congratulations to Amir Kucharski, Dr. Caitlin Scott, and Professor Pete Kekenes-Huskey on the acceptance of their manuscript to the Journal of Physical Chemistry B. The manuscript, titled "Understanding Ion Binding Affinity and Selectivity in beta-Parvalbumin using Molecular Dynamics and Mean Spherical Approximation Theory," will be published in a special edition "Festschrift" in honor of Professor Andrew McCammon, Professor Kekenes-Huskey's former postdoctoral advisor. The abstract is below!

1. Link to article 
2. Abstract:

Parvalbumin (PV) is a globular calcium (Ca2+)-selective protein expressed in a variety of biological tissues. Our computational studies of the rat β parvalbumin (β-PV) isoform seek to elucidate the molecular thermodynamics of Ca2+ versus magnesium (Mg2+) binding at the protein's two EF-hand motifs. Specifically, we have utilized molecular dynamics (MD) simulations and a mean-field electrolyte model (mean sphere approximation (MSA) theory) to delineate how the EF-hand scaffold controls the 'local' thermodynamics of Ca2+-binding selectivity over Mg2+. Our MD simulations provide the probability density of metal-chelating oxygens within the EF-hand scaffolds for both Ca2+ and Mg2+, as well the conformational strain induced by Mg2+relative to Ca2+ binding. MSA theory utilizes the binding domain oxygen and charge distributions to predict the chemical potential of ion binding, as well as their corresponding concentrations within the binding domain. We find that the electrostatic and steric contributions toward ion binding were similar for Mg2+ and Ca2+, yet the latter was approximately 5.5 kcal/mol more stable when internal strain within the EF hand was considered. We therefore speculate that differences in β-PV stability induced by Ca2+ versus Mg2+ binding strongly contributes to the nearly 10,000-fold difference in binding affinity reported in the literature. We further complemented our analyses of local factors governing cation binding selectivity with whole-protein (global) contributions, such as interhelical residue-residue contacts and solvent exposure of hydrophobic surface, that may further contribute to high-affinity cation binding. These contributions were found to be comparable for both Ca2+- and Mg2+-bound β-PV, which may implicate local factors for providing the primary means of selectivity. We anticipate these methods could be used to estimate metal binding thermodynamics across a broad range of PV sequence homologs and EF hand-containing Ca2+-binding proteins.