Conformational and dynamical properties of the niruriside in aqueous solution:: a molecular dynamics approach

The conformational and dynamical hydration features of the niruriside, a compound extracted from the medicinal plant Phyllantus niruri, were investigated in 10 ns molecular dynamics (MD) simulation. Inhibitory activity against hepatitis B has been reported for aqueous extract of P. niruri and, in particular, for the niruriside compound, against HIV replication; making it a natural antiviral candidate. In order to elucidate the niruriside conformational characteristics in water, dihedral angle transitions, intramolecular hydrogen bonds and water bridge formation were monitored. Direct interaction of niruriside with solvent and hydrogen bond formation were analyzed through the radial atomic pair distribution functions. Despite the large number of hydrogen bond acceptor atoms of this molecule, the hydration number was relatively low, indicating poor capacity of water binding. However, simulations showed a great structural stability of this compound in aqueous solution with no evidence of internal hydrogen bonds or water-bridge interactions responsible for preserving its structure. We presume that the intrinsic molecular rigidity results from a combined effect of hydrophilic and hydrophobic interactions. The existence of two hemispherical regions of opposite characteristics provides an amphiphilic nature to the niruriside molecule and brings attention to a possible relationship with its potential antiviral agent function. (C) 2004 Elsevier B.V. All rights reserved.