How Is Bioinformatics Used in Drug Discovery?
Where is bioinformatics useful, and how far does its scope reach?
Bioinformatics covers basically everything related to modern chemistry, biochemistry, and biology. It is mainly known for assembling sequenced genomes, their genomic analyses, and the simulation of various biological processes.
It is also used wherever we try to understand biology, i.e., in analyzing:
- state of the cells, their components, and produced compounds,
- gene expression under given conditions its changes over time and how can we alternate it,
- proteins and other molecules produced in certain types of cells.
Of course, this approach has much more to offer and these are just a few branches of the spreading bioinformatics tree.
Sequencing is understanding - getting to know the genome
Genome analysis is currently one of the most fashionable branches of bioinformatics. Ever since the HGP (Human Genome Project) was started in the 1990s, there has been a particular desire to sequence human DNA and finally learn our own secrets. Recently the scientists finally succeeded! A virtually complete human genome has been sequenced (read about that here). That wouldn't be possible if not for progressing bioinformatic research.
Today, through the genome-wide association study (GWAS), we are looking for variants of genes that may explain differences in populations. And that leads us to a better understanding of how genes contribute to the disease humans are prone to. Which in turn allows for the development of better prevention and treatment strategies.
Study of protein structure - models and simulations
Until recently, complex and costly crystallographic research or magnetic resonance was required to determine protein structure. Currently, thanks to bioinformatics methods, we can predict the protein's structure based on their sequences through credible simulations.
Why is protein structure analysis so important? First of all, because it is closely related to its function and operation. However, the structure of a single protein seemed unknowable, as discussed, e.g., in Levinthal's paradox.
Fortunately, thanks to bioinformatics and the AlphaFold tool's development, we can now get the highest accuracy in protein structure predictions.
The system is trained on several hundred thousand proteins through machine learning, so its predictions are accurate. Even if some parts of the structure seem questionable, the researchers see that clearly, thanks to the built-in internal confidence measure.
Kin to whom? A study of interspecies kinship
One of the many applications of bioinformatics is also studying the interconnectedness of species and determining the kinship between them, which is called molecular phylogenetics.
It helps us understand evolution and how life on Earth has developed through billions of years. Thanks to bioinformatical methods, we can also study the relationships between individual virus variants. That is why, for example, COVID-19 variants and sub-variants have different nomenclature. Rapid sequencing allows scientists to follow the progress of the virus and anticipate outbreaks of new variants.
As a consequence, the pandemic, despite its scale and speed of expansion, could be fairly controlled, and the vaccine was invented relatively quickly.
How can DNA and protein structure analysis help with drug development?
With analysis of crystallographic data or the simulated modeling of a protein from its sequence, a three-dimensional, stable structure of the protein can be obtained. What the researchers are most interested in are the enzymes found in the human body that affect the functioning of vital processes.
Various bioinformatics tools allow the visualization of protein structures and their manual analysis. One of them is Chimera - free of charge for uncommercial use, state-of-the-art, a complex, and highly customizable bioinformatics tool
The study of the structures of molecules allows scientists to create libraries of compounds - authentic databases of billions of molecules. Thanks to the databases of known, small molecules that are synthesizable or occur naturally, a molecule matching the researched receptor can be selected. This is how the researchers can find those therapeutic ligands that are so sought after.
And here we come to the subject of molecular docking.
What is molecular docking
Molecular docking is a technique that predicts the type of interaction between a ligand and the binding site of a protein.
With the help of molecular docking programs (AutoDock Vina, GOLD, MOE-Dock), we can check how the interactions between two molecules, usually the receptor and its ligand, are shaped. It can be achieved by examining different ligands in multiple conformations.
Then researchers can analytically assess whether the ligand molecule matches the receptor and how tightly it binds to it. Thanks to this, they can find potential inhibitors of a given enzyme. Like, for example, COX-2. With reducing COX-2 activity, the inflammation in the body is also reduced.
And this is one of many cases of how manipulating certain enzymes' functioning, the instability of the organism, and illnesses can be controlled or even cured.
How are CADD and bioinformatics different?
CADD, or Computer-Aided Drug Design, about which we wrote in the article: CADD in modern medicine, is the sub-field of bioinformatics. CADD is limited to searching for new or improving current drugs based on computer simulations of their interactions, while bioinformatics is a wider branch of biological and chemical research using computer science.
Bioinformatics for drug discovery - two thrilling use cases
Bioinformatics tools are continuously used to design drugs for various applications.
All this fuss about COX-2
COX-2 inhibitors, already mentioned above, are one of the most exciting inventions in bioinformatics. Previously, we were able to produce COX-1 inhibitors, which allowed us to somehow prevent inflammation. But COX-1 is responsible for many more bodily functions, so its inhibitors had more side effects. Suppressing COX-1 activity is therefore much less safe and involves some unpleasant aftermath.
Due to the synthesis of COX-2 inhibitors, which are primarily responsible for preventing inflammation, it was possible to produce Class III Non-steroidal Anti-Inflammatory Drugs - selective COX-2 inhibitors. These strained the body much less and worked more precisely at the same time.
So all the attention the scientific world is paying to the humble COX-2 enzyme is well deserved. The development of drugs containing its inhibitors has helped many people in the fight against inflammation, which is related to, among others, anti-immune diseases, recurring skin diseases, or allergies.
Anti-aging for real
The search for drugs that act on sirtuins also seems fascinating. These are enzymes that regulate the activity of some metabolic genes, which are presumably associated with aging, life extension, and longevity. So perhaps in a while, we will be able to attempt some age hacking or at least understand the whole mystery of longevity better?
What are the greatest benefits of using bioinformatics methods?
Bioinformatics gives scientists a chance to:
- assemble the organism's genome from DNA sequencers and draw conclusions from it,
- identify compounds present in a given sample by analyzing data from a mass spectrometer.
Without these two fundamental analyzes, it would be impossible to identify and study the genes or proteins found in organisms. Thanks to this, we can quickly and efficiently work on drugs that will respond to the growing needs of an aging society.