Drug Design or Drug Design
Many of us had to take various drugs for medicinal purposes. At the same time, aspirin, Viagra and Tamiflu pharmaceutical companies make billions of dollars. Here are just the tip of the iceberg of drug blockbusters: List of the best-selling drugs of 2010
Let's see how these drugs are currently being developed.
There are 2 basic methods:
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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 (the typical resolution of the listed methods is 1–5 angstroms), it is possible to accurately predict which ligand (here: the term for a chemical substance that binds to a protein) will, for example, “plug” the protein channel in neurons that transmit nerve impulses to the brain. In this way, you can create both instantly killing 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 (and also, often, clusters or supercomputers). There are also competitions among scientific groups where you need to apply your own docking algorithm and solve the problem of speed.
Targets of drugs are of two types: it is either a protein in the human body that functions incorrectly due to various reasons, or an alien microorganism is the causative agent of the disease. If in the first case it is required to improve or compensate for the function of a human protein, then in the second case it is necessary to influence functionally significant proteins of a 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 “anti-influenza” “Relenza”, affecting the neurominidase virus coat protein. Many of the modern anti-HIV drugs have also been developed in this way. They interfere with the work of the viral protease, which cleaves viral proteins and allows the virus to function normally.
In the following, I will describe the principles of NMR spectroscopy, protein crystallography and electron microscopy, as well as explain how to go from the DNA sequence of the protein gene to its three-dimensional structure.
Let's see how these drugs are currently being developed.
There are 2 basic methods:
- Brute force method Every pharmaceutical company has a huge base of chemicals that can potentially affect the human body. Having information about what is happening in the body as a whole with the disease, it can be assumed which substances can help with treatment. This method consists in a simple "screening", that is, the search of all substances and the study of its effects in a particular disease. This way a few decades ago was the only possible and widely used until now. At the same time, incidents sometimes occur. For example, Viagra was originally studied as a drug for people experiencing problems with blood pressure. He didn’t help much to normalize the pressure, but the people taking the drug felt some “side effects” that are now widely known.
- National drug design. This method became available after the development of such methods of studying the structure of proteins 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 variety of functions: they break down fats and carbohydrates (enzymes), participate in the transport of ions (various channels), transmit signals and much, much more. It is proteins that determine how the cell works, and, therefore, the whole organism as a whole. Accordingly, it is very important to understand the molecular mechanism of these machines. In order to understand how proteins work, you need to know their structure.
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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 (the typical resolution of the listed methods is 1–5 angstroms), it is possible to accurately predict which ligand (here: the term for a chemical substance that binds to a protein) will, for example, “plug” the protein channel in neurons that transmit nerve impulses to the brain. In this way, you can create both instantly killing 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 (and also, often, clusters or supercomputers). There are also competitions among scientific groups where you need to apply your own docking algorithm and solve the problem of speed.
Targets of drugs are of two types: it is either a protein in the human body that functions incorrectly due to various reasons, or an alien microorganism is the causative agent of the disease. If in the first case it is required to improve or compensate for the function of a human protein, then in the second case it is necessary to influence functionally significant proteins of a 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 “anti-influenza” “Relenza”, affecting the neurominidase virus coat protein. Many of the modern anti-HIV drugs have also been developed in this way. They interfere with the work of the viral protease, which cleaves viral proteins and allows the virus to function normally.
In the following, I will describe the principles of NMR spectroscopy, protein crystallography and electron microscopy, as well as explain how to go from the DNA sequence of the protein gene to its three-dimensional structure.
Source: https://habr.com/ru/post/142602/
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