Received May 14, 1999

Abstract:

Molecular dynamics simulations in explicit solvent have been performed to investigate the conformational preferences of NAD⁺ in solution. Two simulations, started from different initial conformations, generated similar results. Transitions between different folded forms of the molecule were observed. The simulations predict that the predominant form of NAD⁺ in solution is a folded conformation characterized by a nicotinamide-adenine inter-ring distance of 0.52 nm, an angle of 148 between the aromatic ring planes, parallel glycosyl bond vectors, and the nicotinamide B side facing the adenine ring. Analysis of the NAD⁺ conformations generated during the simulations suggests that folded conformations are favored over extended ones due to the reduction in solvent-accessible surface area, while differences between folded conformations correlate with changes in the solvation properties of the nicotinamide group. The simulation results are consistent with NMR relaxation data, and they argue against previous proposals that intimate, parallel ring stacking is the hallmark of the folded conformation of NAD⁺.

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