Hydration effects on the electrostatic potential around tuftsin

The electrostatic potential and component dielectric constants from molecul ar dynamics (MD) trajectories of tuftsin, a tetrapeptide with the amino aci d sequence Thr-Lys-Pro-Arg in water and in saline solution are presented. T he results obtained from the analysis of the MD trajectories for the total electrostatic potential at points on a grid using the Ewald technique are c ompared with the solution to the Poisson-Boltzmann (PB) equation. The latte r was solved using several sets of dielectric constant parameters. The effe cts of structural averaging on the PB results were also considered. Solute conformational mobility in simulations gives rise to an electrostatic poten tial map around the solute dominated by the solute monopole (or lowest orde r multipole). The derailed spatial variation of the electrostatic potential on the molecular surface brought about by the compounded effects of the di stribution of water and ions close to the peptide, solvent mobility, and so lute conformational mobility are not qualitatively reproducible from a repa rametrization of the input solute and solvent dielectric constants to the P B equation for a single structure or for structurally averaged PB calculati ons. Nevertheless, by fitting the PB to the MD electrostatic potential surf aces with the dielectric constants as fitting parameters, we found that the values that give the best fit are the values calculated from the MD trajec tories. Implications of using such field calculations on the design of tuft sin peptide analogues are discussed. (C) 1999 John Wiley & Sons, Inc.