Conformations of nicotinamide adenine dinucleotide (NAD(+)) in various environments

Enzymes bind NAD(+) in extended conformations and yet NAD(+) exists in aque ous solution as a compact, folded molecule. Thus, NAD(+) conformation is en vironment dependent. In an attempt to investigate the effects of environmen tal changes on the conformation of NAD(+), a series of molecular dynamics s imulations in different solvents was performed. The solvents investigated ( water, DMSO, methanol and chloroform) represented changes in relative permi ttivity and hydrophobic character. The simulations predicted folded conform ations of NAD(+) to be more stable in water, DMSO and methanol. In contrast , extended conformations of NAD+ were observed to be more stable in chlorof orm. Furthermore, the extended conformations observed in chloroform were si milar to conformations of NAD(+) bound to enzymes. In particular, a large s eparation between the aromatic rings and a strong interaction between the p yrophosphate and nicotinamide groups were observed. The implications of the se observations for the recognition of NAD(+) by enzymes is discussed. It i s argued that a hydrophobic environment is important for stabilizing unfold ed conformations of NAD(+). Copyright (C) 2000 John Wiley & Sons, Ltd.