A MOLECULAR MECHANICS FORCE-FIELD FOR NAD(+), NADH, AND THE PYROPHOSPHATE GROUPS OF NUCLEOTIDES

Empirical force field parameters for nicotinamide (NIC+) and 1,4-dihyd ronicotinamide (NIGH) were developed for use in modeling of the coenzy mes nicotinamide adenine dinucleotide (NAD(+)) and NAD hydride (NADH). The parametrization follows the methodology used in the development o f the CHARMM22 all-hydrogen parameters for proteins, nucleic acids, an d lipids. Parametrization of inorganic phosphate for use in adenosine di- and triphosphates (e.g., ADP and ATP) is also presented. While hig h level ab initio data, such as conformational energies, dipole moment s, interactions with water, and vibrational frequencies, were adequate ly reproduced by the developed parameters, strong emphasis was placed on the successful reproduction of experimental geometries and crystal data. Results for molecular dynamics crystal simulations were in good agreement with available crystallographic data.