Computational Biology Computer Aided Drug Designing

High-throughput for Drug Discovery

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High-throughput screening (HTS) is a drug discovery process that allows automated testing of large numbers of chemical and biological compounds for a specific biological target. They accelerate target analysis, as large scale compound libraries can quickly be screened in a cost effective way.

HTS is a computational based useful method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry.


  • Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. 
  • This process can rapidly identify active compounds, antibodies, or genes that modulate a particular bimolecular pathway. The results of these experiments provide starting points for drug design and for understanding the non-interaction or role of a particular location.
  • It is used in drug design and may be used in biological and chemical sciences. This method, due to use of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. 

The HTS method is more frequently utilized in combination with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. 

Drug-drug interactions may contribute to disruption of the normal kinetics of drugs which may result in increased risk of occurrence of adverse effects and as a result affect the clinical development of novel therapeutics. Thus, HTS approaches have been developed in order to determine the activity of chemicals towards modulating the drug metabolizing enzymes. 

High-throughput screening is a widely used method for discovering hits in traditional targets. When it is applied to PPIs. The HTS hit rate is as low as 0.0001% in the identification of JIP-JNK inhibitors. A lot of efforts have been made to build new libraries suitable for PPIs such as peptide libraries, α-helix mimetic libraries, iPPI-DB and natural product libraries. The most widely used HTS techniques for PPIs include the two-hybrid assay, affinity purification, fluorescence polarization (FP), and fluorescence resonance energy transfer (FRET).

One of the advantages with HTS is that it works even when the structure information of a target protein is not available. In addition, HTS can also be applied to show inducible pockets in protein–protein interfaces, as well as allosteric modulators. However, the limitations include the low hit rate due to incompatible libraries and the potential false positives, which need to be eliminated. 

Drug discovery is a highly complex and multidisciplinary process whose goal is to identify new anti-tumoral drugs. The screening attrition rate in the current drug discovery procedures suggests that one marketable drug emerges from approximately one million screened compounds. 

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