### 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 (ΔG_{vdW}) and electrostatic (ΔG_{elec}) 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 ΔG_{vdW} 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.

Original language | English (US) |
---|---|

Pages (from-to) | 3555-3564 |

Number of pages | 10 |

Journal | Journal of Physical Chemistry B |

Volume | 121 |

Issue number | 15 |

DOIs | |

State | Published - Apr 20 2017 |

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### ASJC Scopus subject areas

- Surfaces, Coatings and Films
- Physical and Theoretical Chemistry
- Materials Chemistry

### Cite this

*Journal of Physical Chemistry B*,

*121*(15), 3555-3564. https://doi.org/10.1021/acs.jpcb.6b09528

**Nonpolar Solvation Free Energy from Proximal Distribution Functions.** / Ou, Shu Ching; Drake, Justin A.; Pettitt, Bernard.

Research output: Contribution to journal › Article

*Journal of Physical Chemistry B*, vol. 121, no. 15, pp. 3555-3564. https://doi.org/10.1021/acs.jpcb.6b09528

}

TY - JOUR

T1 - Nonpolar Solvation Free Energy from Proximal Distribution Functions

AU - Ou, Shu Ching

AU - Drake, Justin A.

AU - Pettitt, Bernard

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.

UR - http://www.scopus.com/inward/record.url?scp=85020166856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020166856&partnerID=8YFLogxK

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 Materials

JF - Journal of Physical Chemistry B Materials

SN - 1520-6106

IS - 15

ER -