Drug Development or Drug Design

Many of us had to take various medications for medicinal purposes. At the same time, pharmaceutical corporations make billions of dollars on aspirin, viagra, and tamiflu. Here are just the tip of the iceberg of medicinal blockbusters: List of the best-selling drugs of 2010.

Let's see how such drugs are currently being developed.

There are 2 basic methods:

  1. Brute force method. Every pharmaceutical company has a huge database of chemicals that could potentially affect the human body. Having information about what happens in the body as a whole with the disease, it can be assumed which substances can help with the treatment. This method consists in a simple "screening", that is, enumeration of all substances and the study of its effect in a given disease. This path several decades ago was the only one possible and is widely used so far. In this case, sometimes incidents happen. For example, Viagra was originally studied as a drug for people experiencing problems with blood pressure. He didn’t really help to normalize the pressure, but people taking the drug felt some of the “side effects” that are now widely known.
  2. Rational drug design. This method became available after the development of methods for studying the structure of proteins, such as NMR spectroscopy , protein crystallography, and electron microscopy . The fact is that proteins are the most important biomolecules. In a living cell, they perform a huge number of different functions: they break down fats and carbohydrates (enzymes), participate in ion transport (various channels), transmit signals and much, much more. It is proteins that determine how a cell works, and, therefore, the whole organism as a whole. Accordingly, it is very important to understand the molecular mechanism of operation of these machines. In order to understand how proteins work, you need to know their structure.


GPCR receptor

Determining the structure of proteins is the main idea of ​​modern drug development. After all, knowing the structure of the protein up to the positions of each atom (a typical resolution of the listed methods is 1-5 angstroms), it is possible to accurately predict which ligand (here: the term denoting a chemical substance that binds to a protein) will, for example, “plug” a protein channel into neurons that transmit nerve impulses to the brain. In this way, you can create both an instant kill poison and a cure for epilepsy. The process of calculating the interaction between a protein and a ligand is called docking and requires the use of serious mathematical algorithms (as well as, often, clusters or supercomputers). There are also competitions among scientific groups where you need to apply your docking algorithm and solve the speed problem.

There are two types of drug targets: it is either a protein in the human body that functions incorrectly for one reason or another, or a foreign microorganism - the causative agent of the disease. If in the first case it is required to improve or compensate for the function of the human protein, then in the second it is necessary to influence the functionally significant proteins of the bacterium or virus and block their function. By the way, the well-known antiviral drug Tamiflu was developed using rational drug design. And the first medicine obtained in this way is also the “influenza” Relenza, which affects the protein of the influenza virus envelope neurominidase. Many of today's anti-HIV drugs have also been developed in this way. They interfere with the work of the viral protease, which breaks down the viral proteins and allows the virus to function normally.

In the future, I will describe the principles of NMR spectroscopy, protein crystallography and electron microscopy, as well as explain how to get from the DNA sequence of a protein gene to its three-dimensional structure.

Also popular now: