VIII. Concluding remarks

We have performed QM/MM MD simulations of DNA with a thymine dimer lesion. We have seen that electron uptake by the dimer leads to a rapid breaking of one of the bonds holding the dimer together. There is a barrier for the second bond to break. To accelerate the barrier crossing we have used the flooding technique. From the strength of the flooding potential and the time it took to overcome the barrier, one can estimate an upper bound to the barrier height. If you are interested in this we recommend you to read the papers by Helmut Grubmueller, who has developed the flooding technique.

From the flooding simulation we can infer the reaction mechanism. The flooding trajectory thus provides a good starting point for more advanced methods, such as umbrella sampling, or transition path sampling.

We hope you enjoyed doing this tutorial and that you found it useful for your own work now or in the future. If, while performing QM/MM calculations you run into trouble, or would like to discuss something, you can always contact me.

IX. Further references

1. J. Kästner, H. M. Senn, S. Thiel, W. Thiel, QM/MM Free-Energy Perturbation Compared to Thermodynamic Integration and Umbrella Sampling: Application to an Enzymatic Reaction, J. Chem. Theory Comput. 2006, 2, 452-461

2. H. M. Senn, W. Thiel, QM/MM Methods for Biological Systems, in Atomistic Approaches in Modern Biology. From Quantum Chemistry to Molecular Simulations, M. Reiher (Ed.), Topics in Current Chemistry, vol. 268, Springer, Berlin, 2007, pp. 173-290.

3. H. M. Senn, W. Thiel, QM/MM studies of enzymes, Curr. Opin. Chem. Biol. 2007, 11, 182-187.

4. H. M. Senn, W. Thiel, QM/MM Methods for Biological Systems, Angew. Chem. Int. Ed. 2009, 48, 1198-1229

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VII. The effect of electron uptake II, enhanced sampling with chemical flooding