Molecular dynamics and atomic charge calculations in the study of heparin conformation in aqueous solution Original Research Article

HF/6-31G** and molecular dynamics (MD) simulations were used to evaluate the performance of different atomic charge basis sets (i.e., Mulliken, Löwdin, and Electrostatic Potential Derived Charges—ESP) in heparin simulations. HF/3-21G calculations were also used to study the NMR conformation of the IdoA residue. The results thus obtained indicated that ESP and Löwdin charges gave the better results in heparin simulations, followed by Mulliken charges, and that the minimum-energy conformation of IdoA can be different from that observed by NMR spectroscopy by less than 1 Å. However, it was found that this small conformational modification is capable of inducing a change of almost 200 kJ/mol in the interactions of heparin with the surrounding environment, which is a meaningful amount of energy in the context of ligand–receptor interactions. This information can be potentially of great relevance in the design of heparin-derived antithrombotic compounds.