Editing Globular protein (section)

==Globular structure and solubility==
The term globular protein is quite old (dating probably from the 19th century) and is now somewhat archaic given the hundreds of thousands of proteins and more elegant and descriptive [[structural motif]] vocabulary. The globular nature of these proteins can be determined without the means of modern techniques, but only by using [[ultracentrifuge]]s or dynamic light [[scattering]] techniques.

The spherical structure is induced by the protein's [[tertiary structure]]. The molecule's [[apolar]] (hydrophobic) amino acids are bounded towards the molecule's interior whereas [[Chemical polarity|polar]] (hydrophilic) amino acids are bound outwards, allowing [[dipole–dipole interaction]]s with the [[solvent]], which explains the molecule's solubility.

Globular proteins are only marginally stable because the free energy released when the protein folded into its native conformation is relatively small. This is because protein folding requires entropic cost. As a primary sequence of a polypeptide chain can form numerous conformations, native globular structure restricts its conformation to a few only. It results in a decrease in randomness, although [[non-covalent interactions]] such as hydrophobic interactions stabilize the structure.

===Protein folding===
Although it is still unknown how proteins fold up naturally, new evidence has helped advance understanding.  Part of the protein folding problem is that several non-covalent, weak interactions are formed, such as hydrogen bonds and [[Van der Waals force|Van der Waals interactions]]. Via several techniques, the mechanism of protein folding is currently being studied.  Even in the protein's denatured state, it can be folded into the correct structure.

Globular proteins seem to have two mechanisms for protein folding, either the diffusion-collision model or nucleation condensation model, although recent findings have shown globular proteins, such as PTP-BL PDZ2, that fold with characteristic features of both models.  These new findings have shown that the transition states of proteins may affect the way they fold. The folding of globular proteins has also recently been connected to treatment of diseases, and anti-cancer [[ligand]]s have been developed which bind to the folded but not the natural protein.  These studies have shown that the folding of globular proteins affects its function.<ref>{{cite journal | vauthors = Travaglini-Allocatelli C, Ivarsson Y, Jemth P, Gianni S | title = Folding and stability of globular proteins and implications for function | journal = Current Opinion in Structural Biology | volume = 19 | issue = 1 | pages = 3–7 | date = February 2009 | pmid = 19157852 | doi = 10.1016/j.sbi.2008.12.001 }}</ref>

By the second law of [[thermodynamics]], the free energy difference between unfolded and folded states is contributed by [[enthalpy]] and entropy changes. As the free energy difference in a globular protein that results from folding into its native conformation is small, it is marginally stable, thus providing a rapid turnover rate and effective control of protein degradation and synthesis.