In-vitro enzymatic activity depends on many factors, one of which is the buffering system in the reaction medium. Although essential for a stable pH, buffer agents can have nonetheless a negative influence on enzymatic activity due to effects like destabilization of the enzyme or competitive inhibition of the active site. In practice, the adequate buffer for an enzyme catalyzed reaction is chosen in an experimental test series. We propose a computational method for ruling out buffers in advance to laboratory experiments. Using a docking approach with the new HYDE-scoring function1, we rate buffers by their ability to occupy the active site and block the catalytic amino acids. Buffering agents that are placed with a reasonable interaction pattern into the active site, can reduce the enzymatic activity. We validate our method retro- as well as prospectively on a series of enzymes with experimental assessment of enzymatic activity in different buffer systems.  [1] Reulecke, I., ChemMedChem,   2008  , 3(6)

Computational prediction of enzymatic activity in different buffer solutions

243rd National Meeting (2012)

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