Motive
The method of homology modeling is based on the observation that protein tertiary structure is better conserved than amino acid sequence. Thus, even proteins that have diverged appreciably in sequence but still share detectable similarity will also share common structural properties, particularly the overall fold. Because it is difficult and time-consuming to obtain experimental structures from methods such as X-ray crystallography and protein NMR for every protein of interest, homology modeling can provide useful structural models for generating hypotheses about a protein's function and directing further experimental work.
There are exceptions to the general rule that proteins sharing significant sequence identity will share a fold. For example, a judiciously chosen set of mutations of less than 50% of a protein can cause the protein to adopt a completely different fold. However, such a massive structural rearrangement is unlikely to occur in evolution, especially since the protein is usually under the constraint that it must fold properly and carry out its function in the cell. Consequently, the roughly folded structure of a protein (its "topology") is conserved longer than its amino-acid sequence and much longer than the corresponding DNA sequence; in other words, two proteins may share a similar fold even if their evolutionary relationship is so distant that it cannot be discerned reliably. For comparison, the function of a protein is conserved much less than the protein sequence, since relatively few changes in amino-acid sequence are required to take on a related function.
Read more about this topic: Homology Modeling
Famous quotes containing the word motive:
“The motive of science was the extension of man, on all sides, into Nature, till his hands should touch the stars, his eyes see through the earth, his ears understand the language of beast and bird, and the sense of the wind; and, through his sympathy, heaven and earth should talk with him. But that is not our science.”
—Ralph Waldo Emerson (1803–1882)
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—Ruth Benedict (1887–1948)
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—Henry David Thoreau (1817–1862)