We have compared solvation free energies obtained from a
number of approximate solvation models with an
accurate solution of the Poisson−Boltzmann equation for a large data
set of peptide structures, ranging from
a single amino acid to a peptide sequence of length nine. The
models are assessed for their ability to predict
relative energetics of different 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 approximation to the
Poisson−Boltzmann equation, provides reasonably good solvation free
energies and performs rather well in
rank ordering of conformations. A surface area based model
produces results of intermediate quality. Our
results suggest that the generalized Born model is presently the
clearly preferred alternative if one wishes to
carry out molecular dynamics simulations with a fast, approximate
solvation model.
We present the first analytical gradient Poisson−Boltzmann methodology which is routinely applicable to
large biomolecular systems, such as proteins with sizes ranging from 500 to 5000 atoms. Full minimizations
of several such systems in the gas phase and in solution are contrasted. Because the solvation free energy
term is slowly varying with conformation, it can be evaluated infrequently in the simulation, and hence,
reasonable computation times can be obtained even for large solvated systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.