A molecular mechanics force field for NAD+ NADH, and the pyrophosphate groups of nucleotides

Empirical force field parameters for nicotinamide (NIC+) and 1,4-dihydronicotinamide (NICH) were developed for use in modeling of the coenzymes nicotinamide adenine dinucleotide (NAD+) and NAD hydride (NADH). The parametrization follows the methodology used in the development of the CHARMM22 all-hydrogen parameters for proteins, nucleic acids, and lipids. Parametrization of inorganic phosphate for use in adenosine di- and triphosphates (e.g., ADP and ATP) is also presented. While high level ab initio data, such as conformational energies, dipole moments, interactions with water, and vibrational frequencies, were adequately 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. Simulations of NAD+ in the enzyme alcohol dehydrogenase compared quite favorably with experimental geometries and protein matrix interactions. © 1997 by John Wiley & Sons, Inc.