Heavy elements in AMBER-ii Force Field

In classical bioorganic force fields the Lennard-Jones potential for heterogeneous atoms is determined using the Lorentz-Berthelot combining rules or the rules of geometric mean. This method works well for the "bioelements" H, C, O, N. However, it is well known that such rules are not applicable for heavy elements. This is carefully investigated for noble gases and several other combining rules have been proposed. There are examples of parametrization of bioorganic force fields made on this basis. Nevertheless, the problem has not been finally solved. The combining rules that work well between noble gases poorly describe the interactions of these gases with hydrocarbons¹.

AMBER-ii applies Waldman-Hagler rules for all elements except hydrogen. Hydrogen is regarded as a special element for interactions with which the Lorentz-Berthelot rules are applied. Such a scheme on the one hand allows all nonmetals to be included in the parametrization in a natural way; on the other hand, since the radii of C, O and N are close, parameters of the original AMBER for proteins remain unchanged, with the exception of sulfur that has been reparametrized. Indeed, the effect of the new rules on the evaporation heat of liquids containing H, C, O, N is within 2% (Table 10 in [2]).

Thereby heavy nonmetals were introduced in such a way that almost all the original AMBER parameterization remained unchanged.

¹ Song, W.; Rossky, P. J.; Maroncelli, M. Modeling Alkane+Perfluoroalkane Interactions Using All-Atom Potentials: Failure of the Usual Combining Rules. J. Chem. Phys. 2003, 119, 9145−9162.

² Alexei M. Nikitin, Yury V. Milchevskiy and Alexander P. Lyubartsev AMBER-ii: New Combining Rules and Force Field for Perfluoroalkanes. J. Phys. Chem. B, 2015, 119 (46), pp 14563–14573 DOI 10.1021/acs.jpcb.5b07233