Enzyme recognition is the primary event involved in the interaction of proteins with other proteins and with small molecules such as metabolites and therapeutics. Predicting drugenzyme interactions has direct application for completing genome annotations, finding enzymes for synthetic chemistry, and predicting drug specificity, promiscuity and pharmacology. It is suggested that the secondary structure information plays the major role in determining the drug-enzyme interactions activity. For example, cytochrome P450 (CYP) induction-mediated interaction is one of the major concerns in clinical practice and for the pharmaceutical industry [97] . Induction of CYP1A enzymes with a specific structure-stable state may activate some xenobiotics to their reactive metabolites, leading to toxicity [98, 99] . Amino acid composition and hydrophobicity also contribute considerably to these interactions. An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) have an influence on the antihypertensive response, particularly when using ACE inhibitors (ACEI) [100] , mirroring that the amino acid composition did contribute to the interactions. Hydrophobicity plays a role in determining the coefficients of drug-enzyme interaction energy with the application to drug screening as well as in silico target protein screening [101, 102] .