Proteins are involved in every biological process. It increases the rate of virtually all the chemical reactions within cells. Because of its fundamental properties, drug designing could today control proteins without interfering with their so-called active sites. The active side is nothing but the part of the enzyme where the biochemical reaction takes place.
It is conceptually interesting to control proteins. Allosteric regulation is the best example of it. The regulation of an enzyme by binding an effector molecule at a site other than the enzyme’s active site is called as allosteric regulation. It is particularly important in the cell’s ability to adjust enzyme activity.
To help in the better designing of allosteric drugs, EPFL scientists have developed a new computer model. This computer model could better design and control proteins ‘at a distance’ as well.
The ‘at a distance’ approach is nothing but the allosteric regulation. It shows allosteric pathways for enzymes and other proteins more efficiently.
In allosteric regulation, Most proteins contain parts in their structure away from their active site. They can be targeted to influence their behavior ‘from a distance’.
When an allosteric modulator molecule binds such a site, it changes the 3D structure of the protein. Thus, it affects the fundamental function as it indirectly influences the effects of an agonist or inverse agonist at a target protein.
Similarly, an allosteric drug would also be used at a comparatively lower dose than a drug acting directly on the protein’s active site. It provides more effective treatments with fewer side effects.
Still, it can’t fully understand how a molecule binding on a distant and seemingly unimportant part of a large protein can change its function so drastically. To address such questions, scientists classified it into two types. 1. Hinges that creates scissor-like 3D changes and 2. Shear, which involves two planes moving side-by-side.
Both models do not capture all cases of allosteric effects. So, scientists searched for alternative allosteric architectures. They looked at the structure of proteins as randomly packed spheres that can evolve to accomplish a given function.
When one sphere moves a certain way, this new computer model tracks its structural impact on the whole protein.
Scientists said, “Through this approach, we are able to address several questions that conventional models do not answer satisfactorily. Which types of 3D architecture are susceptible to allosteric effects? How many functional proteins with a similar architecture are they? How it is modeled and evolved in a computer to offer predictions for drug design?”
This new computer model intends new theory for allosteric architectures. It introduces the concept that some certain regions in the protein can act as levers. The lever filters the response induced by binding a ligand and allow for action at a distance.
According to scientists, this computational approach to control proteins can be used to analyze the relationship between co-evolution, mechanics, and function.
In addition to the computer model, scientists even developed a new model. This model can predict the number of solutions, their 3D architectures and how the two relate to each other.