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Comparison of the umbrella sampling and the double decoupling method in binding free energy predictions for SAMPL6 octa-acid host–guest challenges

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Abstract

We calculate the absolute binding free energies of tetra-methylated octa-acids host–guest systems as a part of the SAMPL6 blind challenge (receipt ID vq30p). We employed two different free energy simulation methods, i.e., the umbrella sampling (US) and double decoupling method (DDM). The US method was used with the weighted histogram analysis method (WHAM) (US-WHAM scheme). In the DDM scheme, Hamiltonian replica-exchange method (HREM) was combined with the Bennett acceptance ratio (BAR) (HREM-BAR scheme). We obtained initial binding poses via molecular docking using GalaxyDock-HG program, which is developed for the SAMPL challenge. The root mean square deviation (RMSD) and the mean absolute deviations (MAD) using US-WHAM scheme were 1.33 and 1.02 kcal/mol, respectively. The MAD was the top among all submissions, however the correlation with respect to experiment was unexceptional. While the RMSD and MAD via HREM-BAR scheme were greater than US-WHAM scheme, (i.e., 2.09 and 1.76 kcal/mol), their correlations were slightly better than US-WHAM. The correlation between the two methods was high. Further discussion on the DDM method can be found in a companion paper by Han et al. (receipt ID 3z83m) in the same issue.

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Acknowledgements

The authors would like to thank Gerhard König, John Legato, Minkyung Baek and Chaok Seok for helpful discussion and technical assistance. This work was partially supported by the intramural research program of the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health and employed the high-performance computational capabilities of the LoBoS and Biowulf Linux clusters at the National Institutes of Health. (http://www.lobos.nih.gov and http://www.biowulf.nih.gov.)

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  1. Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Naohiro Nishikawa, Kyungreem Han, Xiongwu Wu, Florentina Tofoleanu & Bernard R. Brooks

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  1. Naohiro Nishikawa
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Correspondence to Naohiro Nishikawa.

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Nishikawa, N., Han, K., Wu, X. et al. Comparison of the umbrella sampling and the double decoupling method in binding free energy predictions for SAMPL6 octa-acid host–guest challenges. J Comput Aided Mol Des 32, 1075–1086 (2018). https://doi.org/10.1007/s10822-018-0166-2

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