Structural biology and drug discovery

Future-Proofing Drug Discovery: The Power of Rational Drug Design

Daniel Benjamin, PhD

CTO, Immuto Scientific Inc.

Drug discovery is an ever-evolving field with new challenges that require innovative solutions. One such solution is rational drug design, a scientific approach that relies on target characterization, especially structural characterization. 

By leveraging the knowledge of a disease or biological target, rational drug design enables scientists to design a molecule specifically targeting and treating the disease, leading to the development of more effective drugs with fewer side effects.

Here, we briefly discuss the power of rational drug design and its transformative impact on drug discovery. We explore how this approach differs from traditional drug discovery methods, delve into the process and techniques involved, and share examples of its successful applications in the development of life-saving treatments. 

Rational drug design vs. traditional drug discovery

Traditional drug discovery methods often involves screening large libraries of molecules without knowing the target and how it works, which can be time-consuming and costly. This trial-and-error approach often leads to a low success rate, as many potential drug candidates fail to demonstrate efficacy or are found to have unacceptable side effects.

Rational drug design, on the other hand, begins by gathering information about the disease and its underlying biology. This information includes studying the structure of proteins involved in the disease, how they interact with other proteins, and how they are affected by changes in the protein structure.

By focusing on the molecular details of a disease, rational drug design can:

  • Increase the likelihood of success — By understanding the target and its role in the disease, scientists can design drugs with a higher probability of being effective and safe, leading to a better success rate in clinical trials.

  • Save time and resources — Rational drug design can streamline the drug discovery process by reducing the number of potential drug candidates that need to be tested.

  • Minimize side effects —By designing drugs that specifically target the disease-causing proteins, rational drug design can minimize off-target effects and unwanted side effects, improving patient safety and treatment outcomes.

  • Enable personalized medicine — Rational drug design can also contribute to the development of personalized medicine, as understanding the molecular basis of diseases can help identify patient subgroups who may respond differently to specific treatments.

The process of rational drug design

Rational drug design relies heavily on structural biology techniques such as X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. This can involve studying the structure of proteins involved in the disease, how they interact with other proteins, and how they are affected by changes in the protein structure. Scientists can use this information to design a molecule specifically targeting the disease-causing proteins. 

The goal is to create drugs that bind only to the specific proteins or enzymes causing the disease, reducing the risk of affecting healthy cells and tissues. More advanced rational design approaches even target specific binding sites on a target, verifying structurally which site will most likely result in high efficacy.

An example of successful rational drug design

The success of rational drug design has led to the development of many essential drugs, including treatments for cancer, HIV, and other diseases.

For example, the drug imatinib, used to treat chronic myelogenous leukemia, was developed using rational drug design. Imatinib targets an overactive enzyme in leukemia cells, causing the cells to stop dividing and die.

A few future applications

Rational drug design can also help future-proof drug discovery by enabling scientists to predict what certain therapeutic moieties will do accurately. 

By understanding the structure of a protein and how it interacts with other proteins, scientists can design drugs that are more likely to be effective and have fewer side effects. This can save time and resources in the drug discovery process, leading to faster development of better drugs.

Other potential implications include:

Better adaptation to emerging health challenges. As new diseases and drug-resistant strains of existing diseases emerge, the ability to rapidly design effective treatments will be crucial. Rational drug design provides a powerful tool for tackling these challenges head-on, ensuring that novel therapies can be developed to address evolving health threats.

Facilitating drug repurposing. By understanding the molecular basis of various diseases and the interactions between drugs and their targets, researchers can identify new applications for existing drugs, maximizing their potential impact on patient health.

Enhancing combination therapies. With a better understanding of the molecular interactions between drugs and their targets, rational drug design can contribute to the development of more effective combination therapies. This can be particularly beneficial in the treatment of complex diseases like cancer, where a multi-targeted approach may be more successful in eradicating the disease and preventing recurrence.

Improving the efficiency of clinical trials. A deeper understanding of the molecular basis of diseases and drug-target interactions can help improve the overall efficiency of drug development by reducing the number of trial failures and speeding up the process of bringing new drugs to market.

More information about rational drug design

If rational drug design is your goal, working with a team with expertise in protein-protein interactions, ligand binding affinity, target engagement, protein conformational changes, and more is essential. Immuto is a one-stop shop solution provider—providing structurally-verified assessments of these critical areas to help accelerate drug discovery and development. By partnering with us, you can leverage the latest scientific approaches and technologies to develop drugs that will improve the lives of millions of people.

Resources and next steps

Download our free white paperHydroxyl Radical Protein Footprinting: A Breakthrough Technique for Epitope Mapping—to see exactly how your development lifecycle stands to gain from the latest techniques.

Explore our technology to learn more about how we’re revolutionizing the drug discovery process and helping our partners tackle previously incurable diseases, and promoting a healthier world. Contact us to learn more and schedule a discovery session.


Daniel Benjamin, PhD

CTO, Immuto Scientific Inc.

Dr. Benjamin is the Chief Technology Officer and co-founder of Immuto Scientific. As the CTO, Dr. Benjamin is responsible for leveraging Immuto’s technological resources and expertise to meet the needs of our customers. As one of the inventors of Immuto Scientific’s PLIMB (Plasma Induced Modification to Biomolecules) technology, Dr. Benjamin spearheaded the design, development, and engineering of the technology. His doctorate research work focused on development the PLIMB technology and proving its application for applications relevant to biopharmaceutical research.

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