Comparison of findings from computations and experiments is a non-trivial task, regardless of the level of calculations (e.g., QM/MM, MD, different QM levels, etc.). It is most challenging to assure that the two address the same event. For example, most QM/MM calculations examine a single reaction step, surpassing a single energy barrier, and using protein structure measured with stable, non-reactive, complex. Most experimental measurements, on the other hand, are conducted on a multi-barrier system and measured rates, for example, commonly encapsulate many events, one of which might be the one examined by the calculation. Examples of successful comparisons of computed and experimental findings will be presented, along with some more questionable cases. The examples will focus on studies of two model enzymes, dihydrofolate reductase and thymidylate synthase (see structures below). The main focus from the experimental prospective will be the assessment of data on a single chemical step within the enzymatic complex kinetic cascade. The conclusions will suggest that comparing absolute values (rates, isotope effects, etc.) is most difficult, and less reliable. However, when studying trends it is more likely to reach coherent conclusions that can support and grant mutual confidence for both calculations and measurements. Such successful interactive comparison is of critical important for both computations and experiments, as one feed the other and all experiments relay of calculations or theory to interpret observables on the molecular level.

Comparing Computed Findings to Experimental Data: Challenges and Opportunities

251st National Meeting (2016)

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