Drug discovery is a time-consuming and complicated process that requires thorough scientific research and investigation. Biotechnology has revolutionized the pharmaceutical industry by providing new tools to discover novel drugs that address different diseases. Two of the most commonly used drug discovery approaches are high-throughput screening (HTS) and rational drug design. In this blog post, we will compare these two approaches and highlight their strengths and weaknesses.
High-throughput screening
High-throughput screening is a methodology that allows researchers to test large collections of compounds (libraries) in a relatively short period. This approach is based on the principle of finding a candidate drug by screening molecules against the target protein or enzyme in vitro. HTS technologies have significantly advanced in recent years and can conduct experiments using thousands or even millions of compounds at once.
The primary advantage of HTS is speed. It allows researchers to screen thousands of chemical compounds and test their properties quickly. As of 2021, records show that over 20,000 active compounds were detected with HTS, and the success rate of optimizing them to potential drugs was about 2-3%[1]. The disadvantage of HTS is that it is a hit-and-miss approach that relies on chance discoveries. Moreover, the process can be costly and time-consuming, making it inefficient when targeting highly specific molecules.
Rational drug design
Rational drug design starts with an understanding of the molecular structure of the target protein or pathway. Scientists use computer-based simulations and may utilize various molecular modeling techniques like virtual screening and molecular docking. By predicting the interaction between known molecular structures and the target protein, scientists can identify potential drug molecules that could interact with the target.
The primary advantage of rational drug design is the precision of the process. Researchers can use computer simulations and structural biology techniques to find highly specific molecules that engage with the target protein. This approach reduces the trial and error process and uses fewer resources in drug discovery. However, rational drug design is a complex process that requires a deep understanding of the biochemical pathways and the target molecule under investigation. Additionally, records show that the success rate of rational drug design stands at about 5% [2].
Conclusion
The choice of approach depends on the specific target, its molecular structure, and the goal of the drug discovery mission. Both high-throughput screening and rational drug design have their strengths and weaknesses. High-throughput screening is ideal for identifying potential drug candidates quickly and can be an efficient approach when there is limited knowledge of the target molecule. On the other hand, rational drug design is suitable for specific targeting and efficiency in drug discovery, making it suitable for the treatment of viral diseases like HIV/AIDS and hepatitis C.
References
- Swinney DC and Anthony J. Nat Rev Drug Discov. 2011 Mar;10(3):229-36.
- Brown N and Sexton T. Nat Rev Drug Discov. 2011 Sep 30;11(10):817-31.