SOLVATION FREE-ENERGIES OF PEPTIDES - COMPARISON OF APPROXIMATE CONTINUUM SOLVATION MODELS WITH ACCURATE SOLUTION OF THE POISSON-BOLTZMANN EQUATION

We have compared solvation free energies obtained from a number of app roximate solvation models with an accurate solution of the Poisson-Bol tzmann equation for a large data set of peptide structures, ranging fr om a single amino acid to a peptide sequence of length nine. The model s are assessed for their ability to predict relative energetics of dif ferent peptide conformations (of the same sequence) as determined from the Poisson-Boltzmann results. We find that the widely used distance dependent dielectric model yields qualitatively erroneous results; in contrast, the generalized Born model of Still and co-workers, an appro ximation to the Poisson-Boltzmann equation, provides reasonably good s olvation free energies and performs rather well in rank ordering of co nformations. A surface area based model produces results of intermedia te quality. Our results suggest that the generalized Born model is pre sently the clearly preferred alternative if one wishes to carry out mo lecular dynamics simulations with a fast, approximate solvation model.