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This webinar marks the start of the BioExcel Virtual Workshop on Best Practices in QM/MM Simulation of Biomolecular Systems.


Multi-scale Quantum Mechanics / Molecular Mechanics (QM/MM) simulations have become a popular method for obtaining mechanistic insights into a variety of biomolecular research areas. However QM/MM techniques rely on approximations such as the size of the QM region, the level of QM theory and the MM description. In order to increase confidence in results from QM/MM simulations these approximations require careful validation prior to simulation. With the exception perhaps of ultrafast photo-induced processes, chemical reaction timescales preclude an unbiased sampling of all available reaction pathways. For this reason, QM/MM calculations are typically combined with enhanced sampling techniques, often along predefined reaction coordinates. In addition to considering the accuracy of the QM/MM model, the sampling techniques involved therefore also require validation for the problem at hand.

Consider enzymes for example – an important component in biotechnology. To systematically improve enzymes for biotechnological applications, a detailed understanding of the underlying reaction mechanism is needed. As the time and spatial resolution required to gain atomistic insights into enzymatic activity have been essentially impossible to achieve experimentally (at least until very recently [1]), most of our current knowledge is based on either inference from extensive experimentation [2] or from computer simulations.

In this first QM/MM Best Practice Workshop webinar I will discuss and illustrate these tricky but essential aspects of performing QM/MM simulation in the context of our own work on biological photoreceptors [3-5] and on ATP hydrolysis in an ABC transporter [6].


  1. A. Fersht, Enzyme structure and mechanism, 2nd ed.; W. H. Freeman & Co.: New York, 1984.
  2. P. Mehrabi, E. C. Schulz, R. Dsouza, H. M. Müller-Werkmeister, F. Tellkamp, R. J. D. Miller, E. F. Pai: Time-resolved crystallography reveals allosteric communication aligned with molecular breathing. Science 365 (2019) 1167–1170
  3. K. Pande, et al: Femtosecond Structural Dynamics Drives the Trans-to-Cis Isomerization in Photoactive Yellow Protein. Science 352 (2016) 725 – 729
  4. D. Morozov, G. Groenhof: Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo-Switchable Fluorescent Protein. Angew. Chem. Int. Ed. 55 (2016) 576 – 578
  5. T. Grän, L. Inhester, M. Clemens, H. Grubmüller, G. Groenhof: The Low Barrier Hydrogen Bond in the Photoactive Yellow Protein: A Vacuum Artifact Absent in the Crystal and Solution. J. Am. Chem. Soc. 138 (2016) 16620 – 16631
  6. M Priess, H. Goeddeke, G. Groenhof, L. V. Schäfer: Molecular Mechanism of ATP Hydrolysis in an ABC Transporter. ACS Cent. Sci. 4 (2018) 1334 – 1343


Gerrit Groenhof

Gerrit Groenhof obtained his MSc and PhD in Biophysical Chemistry at the University of Groningen in the Netherlands. He then joined the Department of Theoretical and Computational Biophysics at the Max Planck Institute for Biophysical Chemistry in Göttingen as a postdoctoral researcher, before starting his own research group there. After that, he moved to Jyväskylä, where he is now a professor at the Department of Chemistry. His research group focusses on the development and application of molecular dynamics simulation techniques for investigating reactivity in complex environments.

Register for webinar

Title: QM/MM Best Practice Workshop: Kick-off webinar

Date: 30 October, 2020
Time: 15:00 CET / 14:00 GMT

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