Most of the diseases arise from protein malfunctions or protein abnormalities. Thus, most of the drugs aim to work on the protein through binding with them at the receptor site. Now, this binding process is actually the most crucial phase for drug designers.
There are a number of factors that influence the proteins drug stability. Let’s explain each of the factors precisely to give you a complete picture of what happens during the successful protein drug stable conformation or failure to attain the same.
Factor #1: factors related to the drug
The drugs are themselves protein molecules mostly. So there are things about the drugs that can affect the binding and stability. For instance,
- The concentration of the drug in the patient’s body
- The physicochemical properties of the drug itself
- Whether there is any affinity of the drug for any specific binding component.
These will matter a lot for ensuring the right and stable bond. In fact, it can lead to protein drug resistance if the lipophilicity of the drug decreases. It will diminish the extent of binding.
Factor #2: Interactions of the drug
The displacement interactions are the frequent competitions between the drugs for the same binding site. This can happen when you receive two drugs at a time and one drug displaces the other from the plasma protein binding site owing to the common affinity for the same binding sites.
If that happens, then the system can be unstable. Besides, there can be other factors like
- Allosteric changes in the conformation of the protein molecules that the drug designers can determine through the Ensemble allosteric model. Competition between body constituents like fatty acids and drugs. Free fatty acids can always create trouble.
Thus, each interaction can be crucial for the potency of the drug.
Factor #3: tissue or protein-related matters
The physicochemical properties of the binding agent or the protein matter a lot in determining the drug and protein stability. In this case, the concentration of the same binding agent or protein will be equally important.
Factor #4: Nature of the patient
If the drug is for you, there are a few factors that will contribute again to the proteins drug stability apart from the ones mentioned above.
- Your gender, age, and body weight
- Intrasubject variability
- State of the disease
As these factors will differ for each patient, the designers have to be very careful while finding the appropriate model for all.
Understanding the level of disease
You will notice that in any discussion related to the drug design., the disease state is always an important factor. The reason is simple. If albumin content decreases owing to renal failure, it will decrease the binding of the acidic drugs. The same applies to the hepatic drugs.
Gain Therapeutics is working on these factors to design the most easily binding drugs.