Correlation of solvent fluctuations with dynamics of simple ligand binding to biomolecular surfaces
We used classical atomistic molecular dynamics (MD) simulations to investigate how and to what extend collective protein-water motions affect the dynamics of ligand binding to a biomolecular surface. Therefore, the free energy surface (i.e. potential of mean force, PMF) along the reaction coordinate was determined via Umbrella Sampling and based on that we obtained static one-body friction/diffusion profiles of the ligand along the reaction coordinate. The reaction coordinate was defined as the distance between the hydrophobic patch of ubiquitin and the ligand (LJ-spere).
We could show that dynamics of the ligand are affected both by the binding affinity in terms of the PMF as well as by internal motions of the protein. Furthermore, the ligand couples to solvent fluctuations in the vicinity of the hydrophobic binding patch of ubiquitin.
After finishing his iMOS Master’s thesis Christopher Päslack started his PhD research in the group of Prof. Lars Schäfer.
Link to Master course in Molecular Sciences and Simulation (iMOS) at Ruhr-University Bochum