Important Effects of the Protein Environment - Insights from Applications

Important Effects of the Protein Environment - Insights from Applications 

There seems to be two major reasons for this improvement in calculated geometries improved hydrogen-bond networks and a better description of metal coordination. Apart from these two effects, we did not find any major changes in active-site geometry that could be attributed to the surrounding protein. 

Selection of an active-site model almost always leads to truncations of the hydrogen-bond network. Upon optimization of the active-site structure, this may lead to the formation of artificial hydrogen bonds that disrupt the structure. Freezing selected coordinates in the active-site model can prevent some of these hydrogen bonds to form. Another remedy could be to include more residues around the metal center, but larger QM models are much more expensive and there will probably still be truncated hydrogen bonds, although further away from the reaction center. 

Instead, including the protein environment in a QM MM description gives a correct and stable hydrogen-bond pattern at a low computational cost. 

In many cases the most interesting results of a computational study are the relative energies of transition states and intermediates because they determine the reaction mechanism. In this section we will try to outline when improved active-site geometries can be expected to have important effects on relative energies. 

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