Pseudosubstrate

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In biochemistry, there are decoy receptors, decoy substrates and decoy RNA. In addition, digital decoys are used in protein folding simulations.

Decoy receptor

A decoy receptor, or sink receptor [1], is a receptor that binds a ligand, inhibiting it from binding to its normal receptor. For instance, the receptor VEGFR-1 can prevent vascular endothelial growth factor (VEGF) from binding to the VEGFR-2[1]

Decoy substrate

A decoy substrate or pseudosubstrate is a protein that has similar structure to the substrate of an enzyme, in order to make the enzyme bind to the pseudosubstrate rather than to the real substrate, thus blocking the activity of the enzyme. These proteins are therefore enzyme inhibitors.

Examples include 3KL produced by vaccinia virus, which prevents the immune system of phosphorylating the substrate eIF-2 by having a similar structure to eIF-2. Thus, the vaccinia virus avoids the immune system.

Digital decoys

In protein folding simulations, a decoy is a computer-generated protein structure which is designed so to compete with the real structure of the protein. Decoys are used to test the validity of a protein model; the model is considered correct only if is able to identify the native state configuration of the protein among the decoys.

Decoys are generally used to overcome a main problem in protein folding simulations: the enormity of the conformational space. For very detailed protein models, it can be practically impossible to explore all the possible configurations to find the native state. To deal with this problem, one can make use of decoys. The idea behind this, is that the native configuration has not to be blindly searched through all possible conformations; the search can be limited to a relevant sub-set of structures. To start with, all non-compact configurations can be excluded. A typical decoy set will include globular conformations of various shapes, some having no secondary structures, some having helices and sheets in different proportions. The computer model being tested will be used to calculate the free energy of the protein in the decoy configurations. The minimum requirement for the model to be correct is that it identifies the native state as the minimum free energy state (see Anfinsen's dogma).

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