Role of water in drug-DNA intercalation

In their multiple direet roles, water molecules can lower the activation energy by stabilizing the transition state by hydrogen-bonding and then providing a proton and a hydroxyl ion. In a more indireet fashion, they can capture and direct the substrate towards the active site for eatalysis. 

The above constitute only a few examples of the extensive role of water in enzyme catalysis. Water probably controls many aspects of enzyme catalysis that continuously occur within biological cells and the number of such instances is enormous. However, our understanding of these phenomena remains poor in most cases, although failure of any enzymatic action can lead to serious consequences. 

Major groove side Minor groove side 

An essential chemical for life processes water in biological functions 

TS (kcal/mol) Intercalated state Minor groove-bound state Experimental 

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