Review of the essentials of computational Biochemistry; importance and implications. (Page 4)

Contents

• Protein Structure function relationships
• Homologs, orthologs and paralogs
• Isoforms and isozymes

Protein Structure function relationships

The ultimate quest in biochemical investigations is understanding the structure-function relationships of many biomolecular reactions. Different proteins perform different function; some perform regulatory, structural, catalytic, storage functions and so on. The function that any protein performs depends on their tertiary structure.

The structural conformation that a particular completely folded protein assumes is such that in its “right environment and condition”, it would undergo a conformational change that will result in bringing about the normal function it performs. This “right environment and condition” includes; the optimum pH and temperature, the presence or absence of cofactors, substrates or products of the reactions, the right kind of solvent or reaction medium, etc.

There is an extensive interaction between the protein and the agents of the “right environment and conditions” before the protein will perform its native function. It is this interaction that is the major quest of many biomolecular studies. The currently available knowledge in this area is very limited. If we have detailed understanding of the interaction that exist between the protein and agents of the “right environment and condition”, it then means that we can easily design any protein that would behave predictably. That would be the bedrock of the computational protein designing.

As we advance more in knowledge, research and computating speed, more information about structure function relationships of protein would become available to us. It would be wise of us to look more deeply, into the analyses and interpretation of currently available knowledge on protein sequence, structure and function, as this could help us to make accurate predictions on structure function relationships of biomolecules.

Homologs, paralogs and orthologs

As noted earlier on, the primary amino acid sequence of a protein determines its three dimensional structures and ultimately its function. This assertion implies that protein with identical amino acid sequence would, most likely perform similar function.

Usually when a new protein is discovered, its amino acid sequence used to perform a comparison search with the amino acids sequence of all known protein. The aim usually is to discover other functions that the protein could perform by virtue of its amino acid sequence

When the similarity search is made on all known protein sequence, it is referred to as a homolog search.

When the similarity search is made on proteins found only in the same specie as the query protein, the list of identical protein obtained from such search are referred to as the paralogs of the query protein.

The list of identical proteins obtained when the query protein is compared against proteins found in all species different from that of the query protein is known as the orthologs.

The Homologs and orthologs of a particular protein can be used to identify both distant and near relatives of the protein.

Isoforms and isozymes

Some proteins have a slight modification in their activity, when they are synthesized in a different part of an organism. These modifications in function occur as a result of differences on the number of amino acid that make up the protein sequence.

The different forms of a particular protein in the same organism, is known as the isoform of that protein. If the protein is an enzyme, it is referred to, as the isozyme of that protein.
Usually, what differs in different isoform of a particular protein is the length of amino acid in its sequence. Some isoform may contain or lack some extra motif or domain that is responsible for the slight modification in the function of that protein. Not all protein has known isoform and some may have more than one isoform.

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