Abstract
An implicit solvent model described by a non-simple dielectric medium is used for the prediction of hydration free energies on the dataset of 47 molecules in the SAMPL4 challenge. The solute is represented by a minimal parameter set model based on a new all atom force-field, named the liquid simulation force-field. The importance of a first solvation shell correction to the hydration free energy prediction is discussed and two different approaches are introduced to address it: either with an empirical correction to a few functional groups (alcohol, ether, ester, amines and aromatic nitrogen), or an ab initio correction based on the formation of a solute/explicit water complex. Both approaches give equally good predictions with an average unsigned error <1 kcal/mol. Chemical accuracy is obtained.
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Acknowledgments
I would like to thank Ulf Ryde for fruitful discussions and valuable comments. I am also grateful to Andreas Klamt for providing me with his lowest energy conformer of mannitol (SAMPL4_001).
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Sandberg, L. Predicting hydration free energies with chemical accuracy: the SAMPL4 challenge. J Comput Aided Mol Des 28, 211–219 (2014). https://doi.org/10.1007/s10822-014-9725-3
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DOI: https://doi.org/10.1007/s10822-014-9725-3