Making a good water model: Molecules do conformationally change when cross from a gas to water solution

Solvation energy calculation is absolutely crucial for a successful binding free energy (IC50) determination. Quantum Pharmaceuticals develops aqueous solvation models and tests them against available experimental data to validate the theoretical approaches.

The graph on the left represents two types of solvation energy calculations compared with experiments. The first series (small circles) are the energy differences on solvation for a set of molecules without conformational changes taken into account. The second set (large squares) is obtained after a single optimization run.

The correlation with the experiment clearly improves after conformational changes calculations. Apparently this does not only mean that the model is good, it also means that the molecules do change structure when inserted into water from the gas phase.