A structure in this blog…

Happy new year!! The passing 2012 admonished me for not explaining the structure in my blog to curious readers. Some words appear repeatedly in this blog; yet it was only yesterday that I realized I never told the story behind using these terms. For example, why “minding our molecules”, and why “curator”…

Here is a list of terms that define the structure of the blog, the idea behind the blog’s title, and its purpose. I promise to update this list of definitions as and when I realize the need for the same:

Our molecules MAKE our universe

Medicinal chemists work with a universe of molecules that is a subset of all the molecules possible in chemistry (refer article). This set is constantly expanding and contracting, just as the theory goes with the boundary of our universe. With the discovery of new drugs or new uses for existing drugs, new drug stars, meteors, dust or planets appear in each ‘anti-disease galaxy‘. Existing stars of each galaxy of drugs may be faded away owing to excessive toxicity or other problems such as drug resistance.

Minding our molecules – we the curator

If we were creator (here, curator) and if we had to work systematically with our universe to create, we have to first place all the cards and the cards’ cards on the table.  Say, we decide to work on anticancer drugs. We need to first study the collection of all the anticancer drugs. This is a galaxy in our universe. A study of the molecules would include a study of the world that each molecule is associated with – their synthesis, administration, effects on the body, their metabolism, their end, the impact their discovery had on the disease, the economics associated with them, etc. The curator would then be someone gathering, analyzing and presenting all these stack of cards.

Paraphrasing Albert Einstein, the creator does not play dice; however, Einstein never said anything about cards…                                                         -Curator

Curators would also need to make sense of all these discrete quanta of information to throw light on the evolution of medicinal chemistry. By constantly minding the stacks of cards and their inter-galactic shuffling (for those tired brains going through this pun over pun write-up, this means one drug = star from a group of drugs for a particular disease = galaxy finding other uses = presence in other galaxies) in parallel and in sequence, we can keep track of the physiology and biochemistry of diseases and their germs. Various virtual studies such as docking studies, structure-activity relationship studies, pharmacokinetic profile studies, the various -omics, etc. are some ways of minding our molecules‘ behaviors in wet-lab experiments and nature.

-Will be updated periodically… visit Minding our molecules/ Blog/ Structure

The substrate, the ‘substrate-like’ and the “others” – part 1

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?

…To be continued…


Antitubercular agents: our molecules list 1 – part 2


Antitubercular Agents: our molecules list 1 – part 1




Antitubercular Drugs: INH mechanism


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Thought: Does heat sink into the body?

We know that heat flows from a hotter to a cooler body.

Hotter body is colored red and cooler body is colored blue. Red block arrows show that heat flows from hotter to cooler bodies.

Hotter body is colored red and cooler body is colored blue. Red block arrows show that heat flows from hotter to cooler bodies.

What will result if the same concept is applied to the human body?

The heat distribution in the human body can be studied by constructing human thermal models (as mentioned in this thesis which gives a good introduction) that account for blood flowing in the core of the body Vs blood flowing to the skin. We know that most of the body heat is dissipated at the skin surface via perspiration (ref.). This helps to keep the skin cool. Heat from within steadily flows to the skin and is removed by sweat. So, we have a school of thought that accounts for flow of heat from the core to the skin. But have there been any thoughts of the flow of heat from the surroundings (e.g., air) to the skin?

i. The human body is substituted for the hotter object in the above figure ii. Environment, skin and body core depicted conceptually.

i. The human body is substituted for the hotter object in the previous figure
ii. Environment, skin and body core depicted conceptually.

When heat reaches the skin from outside as well as from the body’s core, what happens?

Heat exchange between body and environment.

Heat exchange between body and environment.

Where does the heat go? Into the fat?