TY - JOUR

T1 - Nonpolar Solvation Free Energy from Proximal Distribution Functions

AU - Ou, Shu Ching

AU - Drake, Justin A.

AU - Pettitt, B. Montgomery

N1 - Funding Information:
We gratefully acknowledge the Robert A. Welch Foundation (H-0037), the National Science Foundation (CHE-1152876), and the National Institutes of Health (GM-037657) for partial support of this work. We thank the scientific computing staff at the Sealy Center for Structural Biology and Molecular Biophysics for computing support.
Publisher Copyright:
© 2016 American Chemical Society.

PY - 2017/4/20

Y1 - 2017/4/20

N2 - 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 ΔGvdW 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 ΔG for arbitrary molecular systems.

AB - 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 ΔGvdW 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 ΔG for arbitrary molecular systems.

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U2 - 10.1021/acs.jpcb.6b09528

DO - 10.1021/acs.jpcb.6b09528

M3 - Article

C2 - 27992228

AN - SCOPUS:85020166856

VL - 121

SP - 3555

EP - 3564

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1089-5647

IS - 15

ER -