Modeling glycosaminoglycans - hyaluronan, chondroitin, chondroitin sulfate A, chondroitin sulfate C and keratan sulfate

Molecular modeling of glycosaminoglycans, hyaluronan, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate and keratan sulfate is presented. Semiempirical quantum mechanical calculations, PM3 method, have been used to locate the minimal energy regions in the conformational space around the beta1-->3 and beta1-->4 glycosidic linkages. The global minima obtained for each of the glycosaminoglycans correspond to a compact conformation across the beta1-->3 linkage and to the standard extended form across the beta1-->4 linkage. The higher minima obtained around the beta1-->3 linkage reproduces the crystallographic data for hyaluronan. A complex of hyaluronan and hydrated chromium ion has been modeled as well (ZINDO method). The complexation at the beta1-->3 linkage resulted in an extended conformation. (C) 2004 Elsevier B.V. All rights reserved.