title: Nonpolar Solvation Free Energy from Proximal Distribution Functions.
abstract: 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 (ΔG) of a variety of solutes. In particular we use pDFs computed for small peptide molecules to estimate ΔG for larger peptide systems. We separately compute the non polar (ΔGvdW) and electrostatic (ΔGelec) 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 ΔGvdWcalculated 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 ΔG for arbitrary molecular systems.
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , 301 University Blvd, Galveston, Texas 77555-0304, United States.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Ou
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , 301 University Blvd, Galveston, Texas 77555-0304, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Drake
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , 301 University Blvd, Galveston, Texas 77555-0304, United States.
authors.forename: B Montgomery
authors.identifier: 0000-0003-4902-3046
authors.initials: BM
authors.lastname: Pettitt
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D000465:Algorithms; D002073:Butanes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D002073:Butanes; D010455:Peptides; D012997:Solvents; C019529:polyalanine; C011080:polyglycine; C046888:butane; D000433:1-Propanol