Molecular basis of calcium binding by polyguluronate chains. Revising the egg‐box model

The egg-box model is the commonly accepted description of the calcium alginate/guluronate structure. It assumes that calcium ions are bound in the periodic chelation sites located between two polyuronate chains. This study was focused on elucidating the nature of interactions between calcium and polyuronates, responsible for the Ca(2+)-induced association of polyuronate chains in the aqueous solutions. Both molecular dynamics and semiempirical (ZINDO-1/Monte Carlo) methods were used for this purpose. Based on the obtained results, new structural models of Ca(2+)-polyguluronate complexes were proposed both for parallel and antiparallel pairing. Contrary to the classical egg-box model, Ca(2+) ions are coordinated by four carboxyl oxygens from two opposite carboxyl groups belonging to two different polyguluronate chains and, additionally, by four oxygen atoms belonging to water molecules. Such a coordination pattern can be interpreted as the result of competition between water molecules and carboxylic groups of polyguluronate for calcium ions. Other structural details (the network of hydrogen bonds, for instance) are close to those corresponding to the "shifted" egg-box model proposed by Braccini and Pérez (Biomacromolecules 2001, 2, 1089) and remain in agreement with the experimental data.