MPI Campus Seminar: Taming the Thermodynamics of Water in Computer Simulations

Water is a ubiquitous, but often overlooked part of essentially all (simulated) biological systems. However, for many biomolecular processes, such as cold denaturation or other processes associated with the hydrophobic effect, a quantitative understanding of the thermodynamics of solvation is crucial. Typically, it involves a well-balanced interplay between enthalpy and entropy contributions. Unfortunately, accurate absolute entropy values are notoriously difficult to obtain from computer simulations. This problem is particularly severe in the case of solvent entropy contributions, since the diffusive nature of the solvent particles yields a large configuration space that needs to be sampled. To solve the sampling problem, we exploit the permutation symmetry of the identical solvent particles to compress the phase space volume by a factor of N!. Although not altering the physics of the system, the approach ensures that each particle samples only a small fraction of the full configurational space and thereby reduces the sampling problem by the Gibbs factor. We employed a mutual information expansion to obtain absolute solvent entropy values from the permutationally reduced trajectory. The method enables us to assign entropy contributions to the different solvation shells and even to individual solvent particles, allowing us to visualize and enhance our understanding of processes like the hydrophobic effect.