Open AccessSulfation and Calcium Favor Compact Conformations of Chondroitin in Aqueous Solutions
Author(s) -
Olgun Guvench,
Elizabeth K. Whitmore
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.1c01071
Subject(s) - sulfation , chemistry , parametrization (atmospheric modeling) , aqueous solution , chondroitin sulfate , molecular dynamics , chondroitin , polymer , calcium , force field (fiction) , solvent , chemical physics , computational chemistry , organic chemistry , glycosaminoglycan , biochemistry , physics , quantum mechanics , radiative transfer
The effects of sulfation and calcium cations (Ca 2+ ) on the atomic-resolution conformational properties of chondroitin carbohydrate polymers in aqueous solutions are not well studied owing to experimental challenges. Here, we compare all-atom explicit-solvent molecular dynamics simulations results for pairs of O-type (nonsulfated) and A-type (GlcNAc 4-O-sulfated) chondroitin 20-mers in 140 mM NaCl with and without Ca 2+ and find that both sulfation and Ca 2+ favor more compact polymer conformations. We also show that subtle differences in force-field parametrization can have dramatic effects on Ca 2+ binding to chondroitin carboxylate and sulfate functional groups and thereby determine Ca 2+ -mediated intra- and interstrand association. In addition to providing an atomic-resolution picture of the interaction of Ca 2+ with sulfated and nonsulfated chondroitin polymers, the molecular dynamics data emphasize the importance of careful force-field parametrization to balance ion-water and ion-chondroitin interactions and suggest additional parametrization efforts to tune interactions involving sulfate.