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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. February 2002, Volume 1, Number 2, 59-63 |
Calculation of Ionic Bridge Contributions to Homospecific Interactions Mediated by
Proteoglycans
Traian Sulea and Zeno Simon
Internet Electron. J. Mol. Des. 2002, 1, 59-63
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Abstract:
Adhesion proteoglycans containing the g200 acidic glycan are
responsible for speciesspecific cell aggregation in some
sponges. Their homospecific cohesion requires a physiological
concentration of calcium ions, but does not take place in the
presence of magnesium. This suggests that Ca2+-mediated ionic
bridges between the carboxylate groups of the glycan domains
(g200-arms) are responsible for the homophilic interactions of
adhesion proteoglycans. Here we apply computational methods
to predict the strength of such ionic interactions and to explain
the metal ion specificity in the aggregation of adhesion
proteoglycans. Ionic bridge stabilities in water are calculated for
model systems using the solvated interaction energy approach,
which combines a molecular mechanics force field (AMBER)
with a continuum model of solvation (BEM). Solvated
interaction energy calculations show a preference for the
formation of the Ca2+-mediated ionic bridge between two acetate
ions in water in comparison to the Mg2+-mediated interaction,
with a difference in binding free energy of 11.7 kcal/mol.
Addition of the estimated translational entropy of the metal ion
to the calculated solvated interaction energy results in -5.5
kcal/mol per Ca2+-mediated ionic bridge formation between two
carboxylate groups fixed on interacting g200-arms. The
energetic cost due to the loss of conformational entropy during
g200 homodimerization could reach 1200 kcal/mol at room
temperature, while the carboxylate content is about 250 groups
per g200-arm. Binding free energy calculations applied to model
systems reproduced the observed metal ion specificity in the
aggregation of adhesion proteoglycans. The strength and the
number of Ca2+-mediated ionic interactions between glycan
domains are sufficient to overcome the high conformational
entropy costs incurred during homophilic cohesion in order to
produce proteoglycan aggregation.
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