Using molecular dynamics simulations to gain insights into biological processes

Molecular dynamics (MD) simulations have become an important tool to provide insight into molecular processes involving biomolecules such as proteins, DNA, carbohydrates and membranes. The advances in computer power in combination with enhanced sampling techniques have enabled the study of systems that cover increasing spatial and time scales. Here, we present our findings about the conformational behaviour of molecules ranging from peptides to proteins. The effect of posttranslational modifications on the structure can be studied by reverting these modifications in silico, for example for the cytotoxic natural product polytheonamide B that forms an unusual beta-helix. We used kinetic models constructed from extensive MD simulations to rationalize the passive membrane permeability of cyclic peptides, which gained much interest as drug candidates for difficult targets such as protein-protein interactions but often suffer from low bioavailability. A similar approach can be used to study how the interactions between glycans and the protein surface of glycoproteins affect oligosaccharide processing.