Computational protocol: A Computational Study of Calcium(II) and Copper(II) Ion Binding to the Hyaluronate Molecule

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[…] The initial calcium(II) hyaluronate model was constructed as described previously [] with the main difference being the size of the QM region as advances in computer hardware allowed us to define a larger QM region, which substantially improves the reliability of results.The QM region consisted of: a calcium(II) ion, two carboxylate groups from two GCU residues (labelled GCU 39 and GCU 54, respectively), two N-acetyl groups from two NAG residues (labelled NAG 38 and NAG 53, respectively) and six water molecules (labelled HOH 44, HOH 47, HOH 50, HOH 59, HOH 62, HOH 65). To delimit the QM region from the MM region dummy link atoms were used on residues NAG 38, GCU 39, NAG 53 and GCU 54.The QM region was simulated with GAMESS-US using either Hartee-Fock or B3LYP or M06 and using either the basis set 6-31G* and 6-31G(d,p) []. The rest of the system was simulated by molecular mechanics with the CHARMM force field, a constant dielectricity of 1.0 and a cut-off distance of 12.0 Å. All simulations were carried out at 300 K. The minimizations were run for 1000 steps. The trajectories were analyzed and the results were compared to available X-ray data for calcium(II) hyaluranate and EXAFS data for copper(II) hyaluronate [,].Previous experimental data show the overall conformation of the hyaluronic acid does not depend much on the bound ionic species, thus calcium(II) ions can be replaced with copper(II) ions. Calculations were subsequently reran and the results were compared with experimental X-ray data for calcium(II) hyaluronate and EXAFS for copper(II) hyaluronate [,].The computed distances at the end of the minimization were the used to calculate the quotients between the computed distances for a given central atom-ligand pair with the experimental distance from the same pair, afterwards the standard deviation was computed for each combination of method and basis set. The values are collected in for calcium hyaluronate and for copper(II) hyaluronate.For the QM/MM simulations the molecular modeling package CHARMM with the GAMESS-US was used, version c35a2q, and ran on the CROW computer clusters at National Institute of Chemistry in Ljubljana [–]. Molecular graphics were produced using VMD []. […]

Pipeline specifications

Software tools CHARMM, VMD
Application Protein structure analysis
Organisms Dipturus trachyderma