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Assignment of protonation states and geometries to macromolecular structures using Unary Quadratic Optimization

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A method is presented for assigning protonation states and hydrogen atom geometry to macromolecular structures. Tautomer and ionization state (including metal ligation) are taken into account during a large scale free energy optimization. This discrete optimization is performed with a Unary Quadratic Optimization procedure. The thermodynamic theory and the results of several computational validation experiments will be presented.

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Correspondence to Paul Labute.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Hydrogen
  • Free Energy
  • Hydrogen Atom
  • Optimization Procedure
  • Ionization State