Matthias Heyden

We use computer simulations to gain atomistic insights into molecular systems. A main focus of our work is to understand the process of solvation of small solutes (ions, alcohols and metabolites) up to large biopolymers (proteins and nucleic acids). Changes in the solvation free energy contribute to the thermodynamic driving force of biomolecular processes and to kinetic barriers that determine kinetics. This is particularly the case for molecular binding events between ligands and their target molecules, the aggregation of proteins and enzymatic catalysis. In order to understand these processes more deeply and to allow for accurate predictions in the future, we develop novel techniques to spatially resolve local contributions to the solvation enthalpy and entropy of a molecule from molecular dynamics simulations and follow their evolution during a reaction.

Our work also inlcudes the analysis of correlated vibrational motion in biomolecular liquids, which provide rich information on the propagation of energy and local density fluctuations within the system (i.e. sound propagation). Our simulations can be compared to coherent scattering experiments with neutrons or x-rays, but the computer models allow further to isolate the correlations between specific components of the system and to follow time- and space correlations of atomic vibrations with spatial resolution. This provides entirely new insights into the dynamic coupling of low-frequency intermolecular vibrations in liquids and between biomolecules and their surrounding solvent.

In addition, we develop novel methods to simulate biomolecular solutions on a large scale including 100's to 1000's of flexible proteins or polymers. In these simulations the solvent is described implicitly and intramolecular degrees of freedom are approximated by finite-size conformational ensembles. However, we use information from all-atom simulations with explicit solvent molecules to maximize the accuracy of such simulations. These approaches provide us with insights into the complex interactions between biomolecules in realistic, crowded environments resembling the interior of living cells.