# The Human Immunodeficiency Virus

Once a binding pocket of an enzyme, which is important for the progress of a disease, is identified, researcher try to find a small drug molecule that fits both, chemically as well as geometrically, into this detected binding pocket. A good example in the case of HIV is the drug Efavirenz.

The drug molecule Efavirenz (Source: Wikipedia)
Click on the structure shown above to place Efavirenz into the binding pocket! Use the mouse to examine how Efavirenz fits into the binding pocket.

### What is the main difference of HIV to other viruses?

HIV differs from many viruses in that it has very high genetic variability, which means that it is able to adapt to the pharmaceutical treatment very fast. The enzyme reverse transcriptase is able to mutate, which induces resistency for drugs like Efavirenz.

For example if at amino acid position 103 of the reverse transcriptase the amino acid lysine is mutated to another amino acid called asparagine.

The amino acids lysine and asparagine (Source: Wikipedia)
What is the difference of the two amino acids?
Click here, to see position 103 of the amino acid sequence!

The amino acid position 103 is one of the amino acid positions involved in the acitivity of the reverse transcriptase. Since the amino acids lysine and asparagine have different chemical properties, the drug molecule is prevented from binding when lysine is substituted by asparagine. Consequently, the drug is without effect.

Compare both binding pockets with and without mutation.

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