Choosing the right drug candidate for binding is a meaningful process where a variety of factors come into play. Two of those factors are the specificity of binding and strength of binding. Some targets require a much higher binding affinity than others. Some require only a moderate affinity. The same can be said of specificity, where some targets may need a higher specificity, while another may work just fine with a more uninhibited binder. In any case, knowing the therapeutic window during which a specific therapy can be administered safely and effectively, and the characterization of the target is similarly well-known, increases the ease of screening for drug candidates that are expected to be efficacious. Alternatively, when the conditions are reversed and the therapeutic window is unknown or unclear, and the target is similarly characterized to a lesser extent, it becomes necessary to screen a much wider range of binders, perhaps even binders with lesser strength or even lesser specificity to find something that will work effectively.
Another thing to consider is the atomic structure of biomolecules. It is well known that amino acids are considered the building blocks of life. An essential function of amino acids is assembling proteins, which operate nearly every function inside a cell. They can do this via data stored in genes. Recently, researchers discovered that a human receptor protein can detect and identify specific individual amino acids exactly as bacteria do. Essentially, what they discovered was a universal sensor exhibited by various receptors that find and identify specific amino acids through intermolecular interaction within two specific groups of atoms that are universally shared throughout all amino acids. This breakthrough discovery could lead to improvements in drugs created from specific amino acids like GABA.
There are a number of types of equipment with technologies that further our understanding about binders:
Dianthus produces valuable and quality data, has the ability to detect accurate binders via high sensitivity, and furthermore requires less assay development in order to provide quantitative results from real-life samples. Dianthus uses two methods to measure molecular interactions: TRIC and Spectral Shift. As a screening platform, Dianthus is both microfluidics-free and plate-based. With Dianthus, you do not have to worry about aggregation due to high concentrations like you would with isothermal calorimetry. If aggregation does occur at low concentrations, Dianthus is still able to differentiate between binding and aggregation so that molecular behavior can be observed. Measurements are recorded in solution and are also mass-independent, making Dianthus a particularly effective instrument for your more challenging screening projects.
Monolith is another platform that eases the volume requirements of isothermal calorimetry (ITC), leaving more samples available for additional experiments. Monolith also measures Kds varying from pM to mM. By being able to look at both weak and strong molecular interactions, it can meet the demand for many different projects.
Whichever technology is used, the importance of choosing the right candidate cannot be stressed enough. Drug efficacy can suffer if the right candidate is not chosen and choosing the right candidate can be life-changing.