Efficient calculation of SAMPL4 hydration free energies using OMEGA, SZYBKI, QUACPAC, and Zap TK

• Published in: Journal of computer-aided molecular design 2014-03, Vol.28 (3), p.289-298
• Main Authors: Ellingson, Benjamin A., Geballe, Matthew T., Wlodek, Stanislaw, Bayly, Christopher I., Skillman, A. Geoffrey, Nicholls, Anthony
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Chemical compounds; Chemistry; Chemistry and Materials Science; Computer aided design; Computer Applications in Chemistry; Computer Simulation; Dissolution; Errors; Failure; Free energy; Histology; Hydration; Mathematical analysis; Models, Chemical; Models, Molecular; Molecular Conformation; Molecular structure; Morphology; Physical Chemistry; Software; Solubility; Solvation; Solvents; Thermodynamics; Water - chemistry
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-014-9720-8

Several submissions for the SAMPL4 hydration free energy set were calculated using OpenEye tools, including many that were among the top performing submissions. All of our best submissions used AM1BCC charges and Poisson–Boltzmann solvation. Three submissions used a single conformer for calculating the hydration free energy and all performed very well with mean unsigned errors ranging from 0.94 to 1.08 kcal/mol. These calculations were very fast, only requiring 0.5–2.0 s per molecule. We observed that our two single-conformer methodologies have different types of failure cases and that these differences could be exploited for determining when the methods are likely to have substantial errors.