Solvation free energy arithmetic for small organic molecules

Aleksandar Lazaric, Viren Pattni, Kaprao Fuegner, Arieh Ben-Naim, Matthias Heyden

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Solvent-mediated interactions contribute to ligand binding affinities in computational drug design and provide a challenge for theoretical predictions. In this study, we analyze the solvation free energy of benzene derivatives in water to guide the development of predictive models for solvation free energies and solvent-mediated interactions. We use a spatially resolved analysis of local solvation free energy contributions and define solvation free energy arithmetic, which enable us to construct additive models to describe the solvation of complex compounds. The substituents analyzed in this study are carboxyl and nitro-groups due to their similar sterical requirements but distinct interactions with water. We find that nonadditive solvation free energy contributions are primarily attributed to electrostatics, which are qualitatively reproduced with computationally efficient continuum models. This suggests a promising route for the development of efficient and accurate models for the solvation of complex molecules with varying substitution patterns using solvation arithmetic.

Original languageEnglish (US)
Pages (from-to)1263-1277
Number of pages15
JournalJournal of Computational Chemistry
Volume44
Issue number13
DOIs
StatePublished - May 15 2023

Keywords

  • computational drug design
  • solvation thermodynamics

ASJC Scopus subject areas

  • General Chemistry
  • Computational Mathematics

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