DEVELOPMENT & INCORPORATION OF CARBOHYDRATE FORCE FIELDS FOR USE WITH AMBER

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The all atom AMBER force field has been described in detail elsewhere, and it is only necessary here to outline the parameters that most strongly influence the conformational properties of biomolecules. To achieve correct dynamic behavior (conformations and lifetimes), the dihedral parameters are the most important of the valence terms. In the development of the GLYCAM parameters for oligosaccharide simulations with AMBER, we made extensive use of quantum calculations to derive appropriate values for the coefficients, torsional phase shifts, and equilibrium values. Due to the polar nature of oligosaccharides and proteins, electrostatic interactions, determined by partial atomic charges, are as important as the torsion terms. It is essential that these charges result not only in a correct reproduction of relative conformational energies, but also in the correct interaction energies between the biomolecule and its aqueous environment. Although partial charges are a useful model for computing electrostatic properties, they are non-physical and there have been numerous methods employed in their calculation. Within AMBER the partial charges are determined by fitting to quantum mechanical electrostatic potentials (ESP-charges). In light of the developments arising from our parameterization of GLYCAM, to generate a parameter set that performs well on peptides, and that is compatible with the GLYCAM parameters, several properties will have to be addressed. In general, all of the valence terms will continue to be derived from quantum mechanical calculations, mostly performed at the B3LYP/6-31++G** level. But three areas in particular are being reexamined, namely, the use of 1-4 scaling, the inclusion of lone pairs on oxygen, and the complex relationship between 1-4 scaling, torsion terms, electrostatic interactions and charge polarization.