posted on 2007-05-10, 00:00authored byPing Yang, Bernard Spiess, Pushpalatha P. N. Murthy, Richard E. Brown
The binding of the most common metal cations of cytoplasm (Li+, Na+, K+, Mg2+ and Ca2+) to a model
molecule having an intramolecular hydrogen-bonding network, myo-inositol-2-monophosphate, was studied
using first principles. A strong correlation between the conformation of metal inositol phosphate complexes
with the type of metal cation, degree of deprotonation state, and the surrounding environment has been observed.
On the basis of the hydrogen-bonding network analysis of the cation-phosphate complexes (Mn+−Ins(2)P1),
the alkali cations show little effect on the conformational preference while the conformational preference for
the binding of the alkaline earth cations is pH-dependent and solvent-dependent. For example, these calculations
predict that Mg2+−Ins(2)P10 and Mg2+−Ins(2)P12- favor the 1a/5e form while Mg2+−Ins(2)P1- favors the
5a/1e conformation. The Ca2+−Ins(2)P1- complex prefers the 1a/5e conformation in the gas phase and in a
nonpolar protein environment, but inverts to the 5a/1e conformation upon entering the polar aqueous phase.
The binding affinities of the cations and the pKa values for the cation-phosphate complexes are derived from
thermodynamical analysis.