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Native state
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===Proteins=== {{Main|Protein structure}} While all protein molecules begin as simple unbranched chains of [[Amino acid|amino acids]], once completed they assume highly specific three-dimensional shapes. That ultimate shape, known as [[tertiary structure]], is the folded shape that possesses a minimum of [[Thermodynamic free energy|free energy]]. It is a protein's tertiary, folded structure that makes it capable of performing its biological function. In fact, shape changes in proteins are the primary cause of several [[neurodegenerative disease]]s, including those caused by [[prion]]s and [[amyloid]] (i.e. [[mad cow disease]], [[kuru (disease)|kuru]], [[Creutzfeldt–Jakob disease]]). Many [[enzyme]]s and other non-structural [[protein]]s have more than one native state, and they operate or undergo regulation by transitioning between these states. However, "native state" is used almost exclusively in the singular, typically to distinguish properly [[protein folding|folded]] proteins from [[Denaturation (biochemistry)|denatured]] or unfolded ones. In other contexts, the folded shape of a protein is most often referred to as its native "[[Chemical conformation|conformation]]" or "structure." Folded and unfolded proteins are often easily distinguished by virtue of their water solubilities, as many proteins become insoluble on denaturation. Proteins in the native state will have defined [[secondary structure]], which can be detected spectroscopically, by [[circular dichroism]] and by [[Protein NMR|nuclear magnetic resonance]] (NMR). The native state of a protein can be distinguished from a [[molten globule]], by among other things, distances measured by NMR. Amino acids widely separated in a protein's [[primary structure|sequence]] may touch or lie very close to one another within a stably folded protein. In a molten globule, on the other hand, their time-averaged distances are liable to be greater. Learning ''how'' native state proteins can be manufactured is important, as attempts to create proteins from scratch have resulted in molten globules and not true native state products. Therefore, an understanding of the native state is crucial in [[protein engineering]].
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