A substrate is a small molecule (compared to enzymes and receptors, that are macromolecules) occurring in the physiological pathway of an organism that communicates with the protein (whether enzyme, or receptor). A drug is another chemical compound – just another molecule, made of the same old elements as in any other molecule, that is ‘substrate-like’. In general, we agree that the drug resembles the substrate biochemically. But drugs and substrates are also molecules. Like all molecules, they are also subsets of all chemical compounds. In other words, molecules we call “drugs” can interfere with biological systems meant for molecules we call “substrates“.
Substrate + substrate-like + others = all molecules occurring on Earth
Substrates and drugs are different from “others” that are biologically inactive. So what differentiates drugs from other molecules, chemically?
In other words, are there specific combinations of elements that are found among drug molecules but not among “others”?
Can we identify a pattern? Will identifying this pattern help us in eliminating unpromising lead molecules at first sight (leads are those molecules that have potential to become a drug)? This interesting concept is investigated by the research paper:
“Can We Learn To Distinguish between “Drug-like” and “Nondrug-like” Molecules?“; W. P. Walters, M. A. Murcko; J. Med. Chem., 1998, 41 (18), pp 3314–3324.
Does such a study have more to it than that meets the first glance? Lets go way back in time. From the elements of nature, a pool of water with a soup of chemicals formed, that contained self-replicating molecules called coecervates. The pool of chemicals from which all life forms on Earth evolved is basically unaltered. So, there should definitely be a relationship between all chemical compounds found on Earth. Why else would the human body contain orphan receptors?
Orphan receptors: These are those protein molecules that are present in the human body, but have no known natural substrates. The opioid receptors are the typical example.
Opium and other halucinogens have a clear effect on the human body and mind. This is effect is mediated by binding to receptors in the body. However, unlike most other drugs that resemble and compete with natural substrates, opioids do not have an equivalent. For example, It is amazing that the body still holds on to these orphan receptors when there are no innate substrates. The converse is equally amazing – that these receptors respond to substances that are totally foreign to the body. Does the existence of such complementary and biologically active structures belonging to seemingly unrelated groups of molecules serve as a direct evidence for the evolution of organisms from a single source?