Using precomputed near neighbor or
proximal distribution functions
(pDFs) that approximate solvent density about atoms in a chemically
bonded context one can estimate the solvation structures around complex
solutes and the corresponding solute–solvent energetics. In
this contribution, we extend this technique to calculate the solvation
free energies (Δ<i>G</i>) of a variety of solutes.
In particular we use pDFs computed for small peptide molecules to
estimate Δ<i>G</i> for larger peptide systems. We
separately compute the non polar (Δ<i>G</i><sub>vdW</sub>) and electrostatic (Δ<i>G</i><sub>elec</sub>) components
of the underlying potential model. Here we show how the former can
be estimated by thermodynamic integration using pDF-reconstructed
solute–solvent interaction energy. The electrostatic component
can be approximated with Linear Response theory as half of the electrostatic
solute–solvent interaction energy. We test the method by calculating
the solvation free energies of butane, propanol, polyalanine, and
polyglycine and by comparing with traditional free energy simulations.
Results indicate that the pDF-reconstruction algorithm approximately
reproduces Δ<i>G</i><sub>vdW</sub> calculated by benchmark
free energy simulations to within ∼ kcal/mol accuracy. The
use of transferable pDFs for each solute atom allows for a rapid estimation
of Δ<i>G</i> for arbitrary molecular systems
