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Conclusions

In this section we have performed a practical test of the micro-iterative method to locate transition state structures in enzymatic reactions. We have used this method to refine the approximate QM/MM transition state structures obtained using a reaction coordinate method for the racemization of mandelate and propargylglycolate by Mandelate Racemase enzyme found in section 2.3.

The results show that the transition state structures located by means of the reaction coordinate method are, in general, good enough to define a reliable reaction path of the reaction, taking into account both the potential energy barriers and the geometrical structures, provided that a suitable reaction coordinate has been defined for each step of the reaction. However, if the geometrical parameters chosen to define the reaction coordinate in a concrete step do not involve the main geometrical changes that take place in that step, the transition state structure supplied by the reaction coordinate method can turned out to be quite different from the actual one. In this sense the application of a second derivatives direct method, like the micro-iterative, is always recommended, rather to warrant the real nature of transition state of the located structure (in other words, that the located structure lies on the quadratic region corresponding to the actual transition state structure), than to refine the concrete values of the potential energy barriers and the geometrical structure.

Indeed this work concerns just to a particular enzymatic reaction. However, we have tested the racemization of two substrates, that takes place through three different mechanisms, involving many distinct steps. In all, 25 transition states have been located, which provide a critical mass of information, probably enough to think that the conclusions derived here can be quite general for the enzymatic reactions involving thousands of atoms.


next up previous contents
Next: Avoiding the memory problem Up: How important is an Previous: Geometric comparison   Contents
Xavier Prat Resina 2004-09-09