The interrelated topics in drug design and discovery

The ability to design new drugs is dependent on how well we know the properties of “drugs” in general. The most elementary question that needs to be answered is, “what is a drug and how is it different from other chemical and biological substances?”. A rich history of experiments tracing all the way back to the efforts of cavemen have enlightened us on some aspects. Some key points among several are:

1. “what the drug does to the receptors in the body” (pharmacodynamics),

2. “what the body does to the drug given that a drug molecule is an alien” (pharmacokinetics),

3. “what changes do the molecules in the body undergo before and after the intake of a drug” (macromolecular interactions).

Each of these broad areas of research are enriched by studies performed on specific topics. The concept of drug discovery and design in its entirety can be envisioned as depicted in the diagram below:

A Venn diagram showing the organization of topics discussed in this blog

A Venn diagram showing the organization of topics discussed in this blog.

(More on this diagram later)

Given that the field is extensively multidisciplinary, each topic mentioned in  the diagram is not independent of the others. For example the study of protein structures, their dynamic motions, their folding patterns and their sequence – structure correlation (leading to structure prediction) combined contributes to  the study of macromolecular interactions in the body. All these in turn enlighten us on  protein – drug interactions (pharmacodynamic study) that can be applied to drug design. The reverse relationship is also true – there have been examples where the fact that a class of drugs interactions with a certain class of proteins and not others have lead to greater insights on protein structure and dynamics. The way the body works to eliminate the drug (pharmacokinetic study) depends on the level of activity such as, the gene controlled expression levels of a protein, or the active-inactive state  of the protein at a given instant in the body.

Any investigation must face a trade off between the amount of detail one wishes to include and the size of the problem that one considers as “tractable”. For example, when one considers the body, there are a number of unique factors in it that influence ligands (i.e., drugs and other small molecules) and proteins. This influence is sufficiently powerful to change the behavior of each as such and with respect to each other. A good example is the effect that the mere presence of such a large number of molecules (the “soup” of chemicals), the body temperature,  or, say, an enzyme’s activity unique to a race, has on a protein or ligand in the cell, blood stream, etc.

This diagram also gives an idea of how the topics of this blog will be organized.

A Venn diagram showing the organization of topics discussed in this blog
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