Hybrid QM/MM and Related Electronic Structure Methods: Lecture 7

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1 Hybrid QM/MM and Related Electronic Structure Methods: Lecture 7 Jeremy Harvey Winter School in Multiscale Modeling December , KTH Stockholm

2 VI. TS Problems Reaction path optimization In QM/MM can be full of pitfallls Comparison of QM-only and QM/MM models for the mechanism of tyrosinase, T. Borowski and P. E. M. Siegbahn, Faraday Discuss. 2011, 148, 109. unsolved problems for the mechanism of tyrosinase. Recently, another attempt was made to attack the mechanism of tyrosinase 14 with the new X-ray structure as starting point using the the ONIOM version 15 of QM/ MM. In that study a mechanism was found with a low barrier of 16 kcal mol 1, and without the necessity of a nearby base. Rather surprisingly, the mechanism for O O cleavage was exactly the same as one discarded in the previous QM study discussed above. 12 The O O bond was cleaved for an O 2 H ligand bound between the JNH / Lecture 1 2

3 TS Problems Previous QM/MM studypresent QM/MM study Species QM QM/MM QM, BS1 QM/MM, BS1 QM, BS2 QM/MM, BS2 React React (0.0) 0.0 React (1.4) a TS (16.3) a Why the big discrepancy? JNH / Lecture 1 3

4 The TS and Reactant Strcutures found are not Correlated JNH / Lecture 1 4 0

5 Conclusions Calculations have been carried out to clarify the discrepancy between previous QMonly and QM/MM studies on the mechanism of tyrosinase. The QM-only study used a rather small model, while in the QM/MM study the entire enzyme was included. Two important conclusions can be drawn from the results reported here. First, the most likely explanation for the discrepancy between the previous QM and QM/MM results is that the previous QM/MM geometry optimization has converged to an incorrect reactant state. A contributing factor to the discrepancy is also that quite different local minima, with very different energies, were obtained for the points along the reaction pathway. The second conclusion is that the effects of the enzyme outside the QM-model are negligible once the correct calculations have been carried out. With the present result, the mechanism where an O 2 H ligand is ho- JNH / Lecture 1 5

6 QM/MM and Other MultiScale Methods: A Summary Scientific Background on the Nobel Prize in Chemistry 2013 DEVELOPMENT OF MULTISCALE MODELS FOR COMPLEX CHEMICAL SYSTEMS

7 QM/MM JNH / Lecture 1 7

8 σ and π JNH / Lecture 1 8

9 Coarse Grains JNH / Lecture 1 9

10 Other Hybrid Methods There is an increasing tendency to use more sophisticated hybrid methods, broadly characterizable as QM/QM methods In these approaches, the core and environment interact in a more rigorous QM way with one another One example: embedding methods JNH / Lecture 1 10

11 Chemistry Models Models of chemistry are pretty much always multiscale in one sense: they include atomistic-level aspects and macroscopic ones Often these two (or more) levels are integrated conceptually but not within a single computational framework The overhead in computational complexity involved in making models that do carry out the latter integration is considerable But sometimes it is needed and it is also good fun!

12 Thank You!