Calculating gas phase energies of an α(1–4) linked disaccharide: electronic structure theory and classical atomistic simulation

Abstract

As an alternative to time consuming force field development for biomaterials simulation, we here test the ability of the existing condensed matter force field COMPASS to accurately calculate the structure/energy relationship for 24 conformers of an α(1–4) linked disaccharide by comparison to high level electronic structure calculation. As a prerequisite to the COMPASS comparison we compared several different electronic structure approaches in an attempt to determine the optimal method, from a price/performance point of view, for the evaluation of disaccharide structure/energy relationships. Following prior workers, we assumed that relative energies produced using the empirical hybrid generalized gradient approximation (GGA) density functional, B3LYP, paired with the 6-311++G(d,p) basis set are accurate and compare these results to those obtained using Hartree-Fock (HF) theory and the nonempirical GGA density functional of Perdew, Burke and Ernzerof (PBE) with a variety of basis sets. We find that, as expected, HF theory is the worst option of the three (with a mean unsigned error (MUSE) > 2× the other methods) and that the error compensation usually invoked as a justification for employing HF/6-31G(d) in studies of sugar systems only occurs in a small subset of the results. Both the B3LYP and PBE functionals show the same systematic improvement with respect to increasing basis set size: significant improvement comes only with the inclusion of diffuse functions on heavy atoms for the energy calculation portion of the work. However, the MUSE of PBE appears to converge to 0.2–0.4 kcal/mol relative to the B3LYP reference with increasing basis set size, raising possible questions about the ability of B3LYP to accurately describe hydrogen bonding in sugars. We further find that COMPASS provides relatively accurate calculated energies for our suite of test conformers, reproducing the reference electronic structure energies to within an average error less than 1 kcal/mol. These results suggest that COMPASS may be useful in the simulation of the interaction of polysaccharides in aqueous solution and inorganic materials.