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. 2009 Apr 27;5(5):1315-1327.
doi: 10.1021/ct9000608.

CHARMM Additive All-Atom Force Field for Acyclic Polyalcohols, Acyclic Carbohydrates and Inositol

Elizabeth Hatcher  1 , Olgun Guvench, Alexander D Mackerell Jr
Affiliations

CHARMM Additive All-Atom Force Field for Acyclic Polyalcohols, Acyclic Carbohydrates and Inositol

Elizabeth Hatcher et al. J Chem Theory Comput. .

Abstract

Parametrization of the additive all-atom CHARMM force field for acyclic polyalcohols, acyclic carbohydrates and inositol is conducted. Initial parameters were transferred from the alkanes and hexopyranose carbohydrates, with subsequent development and optimization of parameters unique to the molecules considered in this study. Using the model compounds acetone and acetaldehyde, nonbonded parameters for carbonyls were optimized targeting quantum mechanical interaction data for solute-water pairs and pure solvent thermodynamic data. Bond and angle parameters were adjusted by comparing optimized geometries to small molecule crystal survey data and by performing vibrational analyses on acetone, acetaldehyde and glycerol. C-C-C-C, C-C-C-O, C-C-OH and O-C-C-O torsional parameters for polyol chains were fit to quantum mechanical dihedral potential energy scans comprising over 1500 RIMP2/cc-pVTZ//MP2/6-31G(d) conformations using an automated Monte Carlo simulated annealing procedure. Comparison of computed condensed-phase data, including crystal lattice parameters and densities, NMR proton-proton couplings, densities and diffusion coefficients of aqueous solutions, to experimental data validated the optimized parameters. Parameter development for these compounds proved particularly challenging because of the flexibility of the acyclic sugars and polyalcohols as well as the intramolecular hydrogen bonding between vicinal hydroxyls for all of the compounds. The newly optimized additive CHARMM force field parameters are anticipated to be of utility for atomic level of detail simulations of acyclic polyalcohols, acyclic carbohydrates and inositol in solution.

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Figures

Figure 1
Figure 1
Acyclic polyalcohols, acyclic carbohydrates and inositol. In the linear compounds, C1 is at the topmost position of the carbon chain; the aldehyde and ketone functionalities at C1 and C2 in D-allose and D-psicose, respectively, are in bold italics. In inositol, the C1 and C2 position are indicated with 1 and 2, respectively. Those compounds not designated with a D are meso compounds.
Figure 2
Figure 2
Allitol-water interaction orientations used for the water interaction calculations. VMD is used to prepare the molecular graphics.
Figure 3
Figure 3
(a) QM and MM potential energy scans for C-C-C-C, C-C-C-O, C-C-O-H, OC-C-O dihedrals for all n=6 polyols (∼1730 conformations). QM scan is black; MM scan using optimized parameters is red; MM scan using parameters set to zero is blue. QM data have been offset using the global minimum as E=0. MM scans have been root-mean square aligned with the QM scan (i.e. offset by the constant c given in Equation 2). (b) EMM-EQM using the optimized parameters (red) and parameters set to zero (blue).
Figure 4
Figure 4
QM and MM potential energy scans for dihedrals C1-C2-C3-C4, C4-C5-C6-O6, O1-C1-C2-O2 in glucitol, C1-C2-C3-C4 dihedral in erythritol, C1-C2-C3-C4 dihedral in inositol, and O1-C1-C2-C3 dihedral in allose. QM results are black. The MM results, calculated using the optimized parameters, are red.
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