Designing an antivenom in 3D

Atrolysin, the venom of the Crotalus atrox, better known as the western diamondback rattlesnake, is very nasty. It is responsible for the largest number of deaths by snake bites in the United States of America per year. The venom, a metalloproteinase, is an enzyme that breaks down the protective coating of blood vessels. This causes serious internal bleeding in the victim, leading to death. Needless to say, a suitable antidote is urgently needed.

In this bioinformatics practicum, we will design such an antidote by looking at the 3D structure of atrolysin in a number of exercises.

The spatial structure of a protein is very important for its function. Understanding it is the key to solving problems caused by malformed proteins (like we find in many hereditary diseases) or, like in our case, by unwanted malignant proteins in our bodies. You need some background knowledge of protein structure, amino acids and molecular interactions like hydrogen bonds for this practicum.

Exercise 1:

You have seen the primary structure of the protein: the amino acid sequence. This primary structure leads to a specific tertiary (or 3D) structure, which is very important for the function of the protein. A protein with the wrong primary structure and hence the wrong tertiary structure may work poorly or even not all. However, small changes in primary structure do not necessarily lead to an inactive protein. Some amino acids are more important than others in the protein. Extensive mutation studies and so-called multiple sequence alignments are used to investigate which amino acids are most important, and which ones are less important.

Explain why systematically mutating all the amino acids of a protein, one by one, can resolve which amino acids are important?

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