Proteins are large molecules composed of smaller chemical units (residues), the 20 naturally occurring amino acids, stably linked together in an ordered linear sequence. The amino acids possess distinct sizes, shapes, and mutual interactions. Consequently, the ordered sequence (denoted by "primary structure" of the protein) controls physical and biological properties. In its simplest form, "the protein folding problem" consists in predicting the three-dimensional stable shape of protein molecules from the primary structure, to facilitate understanding those physical and biological properties.
While the fixed chemical structure of proteins constrains most of their chemical bond lengths and the angles between neighboring chemical bonds to lie within tight limits, a substantial number of degrees of freedom describing the local amino acid packing ("secondary structure") and the overall three-dimensional shape of the protein (its "tertiary structure" or "conformation") remain to be determined. It is believed that the conformation holds the key to physical and biological properties. An experimentally important type of information relevant to a protein's preferred conformation is a set of distances between selected amino acids.
The folded conformation of a protein is analogous to the posture of a human body. Body motion at skeletal joints plays the role of protein backbone and amino acid side chain folding degrees of freedom. Given a selected set of distances between skeletal joints, for instance, one might be able to infer what posture the human subject had adopted or at least to rule out several possibilities. Similarly, distance geometry for proteins can be used to reconstruct their three-dimensional conformation.
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