| Summary: | Under suitable conditions an unfolded protein molecule refolds spontaneously into a precise three-dimensional shape (known as its conformation), which is fixed by the chemical structure of the molecule. Can the relationship between the shape and chemical sequence of a protein ever be fully understood? I still cannot answer this question, which has troubled me for several years. It may seam surprising that one can work on a problem that could be insoluble. My reasons are as follows: Firstly, the folding problem is the most fundamental problem of theoretical molecular biology. Life is ordered in space and time: a body is an ordered aggregate of cells; a cell is an ordered aggregate of macromolecules; and a macromolecule is an ordered aggregate of atoms. The building blocks of living matter are highly ordered protein molecules, which also use their precise shapes to catalyse the biochemical reactions that make life dynamic. Proteins are to life sciences what the atom is to physics and chemistry. When physical laws determine how the thousands of atoms of a protein fold from a random coil into a precise three dimensional arrangement, dead matter comes to life. The complex order that is found in proteins is unknown in physics or chemistry; it is as if a motor car assembled itself when all the pieces were joined in a line and shaken about. Using electronic computers it may be possible to mimic nature and calculate how the amino acid sequence determines the folded shape of a protein. Apart from many practical uses, a general solution to the folding problem would be fundamentally important.
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