In life, we all want big things, whatever subjective thing it may mean to us a promotion, a new job, more funding for company or expansion somewhere new, but we all strive to achieve something big. When we focus on that big thing, we may lose sight of what it actually entails. How do we actually go from point A to point B? We do not just jump there, although that is a possibility, it is a rare one. More often than not, we get there step by step, thus we must focus on the small things to lead to big results. I have written an article about how consistent 1% improvement led a cycling team to an Olympic Gold medal.
In this article, I’d like to focus on how the small things, the details on the very granular level, drive big events. Many examples of that are clearly seen in science, but one interesting example of that is how the single water molecule could play a crucial role in a eradication of amyloid beta proteins which have been shown to play a crucial role in the progression of Alzheimer’s diseases and dementia in patients. The formation of these plaques is attributed to a cleavage of a certain protein by an enzyme known as BACE1.
One approach to eradicating Alzheimer’s is to find ways to inhibit the function of BACE1. To do so a substrate, or a small molecule, must get inside the active site of the enzyme in order to bind to it and inhibit its function. The structure of this enzyme is such that it has the active site covered by an antiparallel hairpin- loop known as a flap. You may ask: what is an active site? An active site of an enzyme is a region where reactions can happen between the enzyme and other chemical substances. Thus, substances have to get inside there in order to inhibit it or react with it. If the flap is closed, no substances can get inside the active site. So you may ask what drives the opening and closing of the flap? And the answer is that it boils down to a reaction with one water molecule.
In the above image, we see the complex enzyme as well as the active site pictured here. The active site is composed of two residues, or biochemical building blocks, known as Asp 228 and Asp 32. These two residues undergo chemical reaction through a mechanism where one water molecule cleaves the bond between the two residues, thereby releasing energy and changing the conformation of the enzyme which allows for the opening of the flap. Once the flap is open, small substances can enter and bind to the enzyme and inhibit its functioning. This has been an active area of research that uses small molecule designed to prevent the function of this enzyme and thus the formation of the beta-amyloid plaques which are shown to correlate with the degree of dementia in patients.
What is incredible about that is that one water molecule can have huge implications on the functioning of the enzyme and thus the disease it is thought to cause. Do you know how many water molecules are in a glass of water? There are 6.6855 × 1024 molecules in a glass of water! But you only need one water molecule to make this happen. Thus, when we think about the things we want to achieve – the big grand things in our way, we should first focus on the smaller and finer details that drive the process. Here in this example, we can see it is a single water molecule, a tiny thing but has a huge impact. The same thing in careers and so on, we have to look at the small things that are the root cause and drivers of change. So focus on the details behind the grand events or changes you envision in order to make them happen. As seen in this example, a tiny thing has a powerful effect.