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Throughout most of the history of medical science, new drugs have been discovered though a process of trial-and-error or simply through sheer luck. As the demand for new and more effective drugs has increased, a new method of drug development called rational drug design has begun to replace the old methods. In rational drug design, biologically active compounds are specifically designed or chosen to work with a particular drug target. Rational drug design often involves the use of molecular design software, which researchers use to create three-dimensional models of drugs and their biological targets. For this reason, the process is also known as computer-aided drug design.
A drug target, or biological target, is usually one of two types. The first type is a molecule in the human body that causes disease when it is defective in some way. The second is a molecule from a disease-causing microorganism. Drug development involves discovering or designing new chemical compounds that interact with these targets in a beneficial way, such as by interacting with cholesterol to remove it from the body or by interacting with a virus to cause its death.
Older methods of developing new medications have several flaws that make drug discovery an expensive business. The easiest and fastest method of developing a new drug is simply to discover, through sheer luck, that a certain compound is biologically active against a drug target of interest. Perhaps the most famous such incident was the discovery of penicillin by Alexander Fleming in 1928. The microbiologist discovered the first antibiotic when some bacterial cultures he was working with became contaminated with a bactericidal fungus. Of course, this type of chance discovery does not happen very often, and luck is not something that drug companies rely on for the development of new medications.
The most common method used to develop new medications is a lengthy, large-scale process called combinatorial library screening. In this process, large numbers of chemical compounds are created and then screened for biological activity. If a given compound shows signs of interacting with a biological target, it receives further attention and might be developed into a new drug. This process can take many years and enormous amounts of money, though, and even at the end of the development period, the drug might not be effective enough or safe enough for human use.
Rational drug design is a more streamlined process that requires careful consideration of the target of the drug as well as the drug itself. This method of drug design uses special equipment to examine the three-dimensional structure of a drug target and then find a compound that can interact with the target. Rational drug design therefore requires significant knowledge of chemistry as well as biology, because chemical interactions between drugs and their targets are what determine whether a drug is biologically active.
Compounds can be located for testing in two ways. The first involves the use of combinatorial library screening. In this case, however, the process is streamlined because researchers using rational drug design methods will screen the library for compounds of a shape that is specific enough to interact with the drug target of interest. The second method involves the actual design of a compound that can interact with the target. This requires consideration of the chemical makeup of the compound and knowledge of what chemical groups the compound might require in order to be capable of interacting with the drug target.
The first drug developed using a process of rational drug design was an antiviral drug called Relenza®. This drug was designed to interact with an influenza protein called neuraminidase. Without this protein, the influenza virus cannot infect new cells; therefore treatment with the drug can shorten the duration of the illness. Other rationally designed drugs include HIV drugs such as ritonavir and indinavir, both of which interact with viral proteins called proteases.