SAMPL2 challenge: prediction of solvation energies and tautomer ratios

This special issue reports on the third annual Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) challenge and workshop. The SAMPL2 challenge was open to all and allowed participants to make blind predictions of tautomer ratios and small-molecule hydration energies. Participants were asked to make specific predictions of experimental values that were not readily available. In order to maximize participation in SAMPL2, the challenge was announced at several conferences and on CCL (ccl.net, the computational chemistry list), and practitioners who had published articles about tautomer prediction or transfer energies within the last few years were invited directly. Prior SAMPL challenges covered transfer energies, affinity predictions, virtual screening and protein-ligand co-crystal pose prediction and have been discussed elsewhere [JMC 2008, 51(4):769–779; JPC B 2009, 113(14):4501–4537]. This introduction will comment briefly on the results from SAMPL2, discuss the importance and design of prospective predictions, and introduce the next challenge, SAMPL3.

The SAMPL2 evaluation was carried out in the spring of 2009 and discussed at a workshop help at McGill University in Montreal in June of 2009. This issue contains ten papers covering the results of the challenge and an eleventh manuscript will appear soon in JCAMD’s special issue on Tautomers. The first paper is an overview of the data sets, methods of analyzing performance, and a perspective about the ability of computational chemists to correctly estimate these relatively simple experiments. The SAMPL organizers report that transfer energies can reliably be predicted with between 1 and 2 kcal/mol accuracy but that similar accuracy in prediction of tautomer ratios requires computationally intense quantum-mechanical calculations, even for the simplest of tautomeric molecules. The following nine manuscripts describe individual efforts and include the very wide variety of solvation models currently under active development in the computational community, including all-atom explicit water simulations and, single- and multi-conformer implicit solvent models either with or without integrated quantum-mechanical calculations. The methods also included static charge models fit by a variety of methods and levels of theory as well as multiple approaches to solute polarizability. Despite the panoply of methods, it is encouraging to see that in many cases, the theoretical approaches produce similar results, and in some cases may even suggest the need to reexamine the experimental data.