Atomistic Simulations


Molecular modeling and simulations can be used to gain insight in the behavior of molecules. For some molecular systems an abstraction can be made from the atoms (coarse graining) to yield more general results, either because this information is sufficient or the size of the system under investigation is too large to allow a more detailed investigation. However, often the required information or answers to a research question are governed by changes on the atomic level. For those problems, which typically originate from (bio)chemical research, full atomistic modeling and simulations are a prerequisite. Below, a few examples are shown:

  • Protein modeling: one can determine the three dimensional structure of a protein, from scratch or based on the structure of known proteins from the same family via homology modeling.
  • Docking: in order to find ligands which will inhibit a certain enzyme, docking experiments yield binding energies of small molecules in these enzyme and can help to find potential drugs.
  • Protein-protein interactions: some proteins are activated by interactions with other proteins; modeling can help to gain insight in the underlying mechanisms.
  • Host-guest interactions: in the field of supramolecular chemistry many system have been devised which mimic nature and help to acquire knowledge on the workings of the cell. The image shows a fifth generation propyleneimine dendrimer (left), a host-guest complex of such a dendrimer with appropriate guest molecules (middle), and a detailed view of some host-guest interactions (right). Molecular dynamics simulations can calculate the time evolution of such supramolecular systems and, hence, reveal their dynamic behavior.

Since many of the research topics specified above stem from the pharmaceutical of supramolecular chemistry field, the projects covering these topics are often a cooperation of our group with a chemically oriented company or group, such as Organon or SMO.

Drug design

An important application of molecular modelling can be found in the field of medicine design. Molecular dynamics simulations are often used to investigate the dynamic properties of protein-ligand interactions. The flexibility of the ligand in a protein active site can help identify which ligand substituents have a suboptimal interaction with the protein. An iterative process of modifying such substituents followed by MD results in more stable protein-ligand interactions and thus more potent medicines.

In the picture you can see that the substrate (left) has a predominant interaction with the protein (top), as well as two conversion sites (bottom). A modification in the upper region and a modification of the conversion sites creates an inhibitor (medicine) which interacts stronger with the protein (top) and possesses a more pronounced ring stacking (right).


  • T. Chang, K. Pieterse, M.A.C. Broeren, H. Kooijman, A.L. Spek, P.A.J. Hilbers, E.W. Meijer, Structural Elucidation of Dendritic Host-Guest Complexes by X-ray Crystallography and Molecular Dynamics Simulations, Chem. Eur. J., 13(28), 7883-7889, (2007)
  • L. Roumen, M.P.A. Sanders, K. Pieterse, P.A.J. Hilbers, R. Plate, E. Custers, M. de Gooyer, J.F.M. Smits, I. Beugels, J. Emmen, H.C.J. Ottenheijm, D. Leysen, J.J.R. Hermans, Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics, J Comput Aided Mol Des, 21(8), 455-471, (2007)
  • J. van Buijtenen, B.A.C. van As, M. Verbruggen, L. Roumen, J.A.J.M. Vekemans, K. Pieterse, P.A.J. Hilbers, L.A. Hulshof, A.R.A. Palmans, E.W. Meijer, Switching from S- to R-Selectivity in the Candida antarctica Lipase B-Catalyzed Ring-Opening of omega-Methylated Lactones: Tuning Polymerizations by Ring Size, J Am Chem Soc, 129(23), 7393-7398, (2007)


If you have any questions about the research presented on this page, you can contact Peter Hilbers or Bart Markvoort.