Molecular dynamics study of the Mg - AMP interaction in water

The conformational states of $Mg^{++}$ complexed with adenosine monophosphate (AMP) in water solution is analyzed using classical molecular dynamics (MD) simulations. Relevant portions of the 3D \textit{potential of mean force} (PMF) of $Mg^{++}$ is reconstructed by employing two distinct methods: (1) equilibrium MD simulations using the umbrella sampling and weighted histogram analysis method, and (2) non-equilibrium steered MD simulations using a recently developed method based on the Jarzynski equality. Withing computational errors, both methods yield the same results. Two topologically distinct sets of equilibrium conformations of $Mg^{++}$ in the vicinity of the phosphate moiety are found. The free energy difference between the states within a given set is about $1~kT$, and are separated by potential barriers of $\sim 10~kT$ in height. However, the free energy difference between states from the two distinct sets are found to be unrealistically high ($\sim 10~$kcal/mol). Also, the calculated dissociation energy of Mg++ from AMP exceeds several times the corresponding experimental value. Possible sources of this discrepancy are discussed, and alternative methods to improve the accuracy of the calculations are proposed.