Molecular docking in drug discovery
When we fall ill, doctors prescribe
medications. Today, a plethora of medicines are available for various ailments
in the market. However, behind every commercially available drug lies a lengthy
journey, often concealed, involving the diligent efforts of numerous
scientists, individuals, and industries.
The cornerstone of discovering
these drugs is molecular docking, which plays a pivotal role. Presently, even
before formulating a medicine, its effects and potential side effects can be
ascertained without the need for extensive clinical trials. This advancement is
attributed to molecular docking. Let's delve deeper into the concept of
molecular docking.
What is molecular docking?
The term "docking"
denotes the process of aligning or examining the interaction between any two
molecules. Although the concept of molecular docking may appear intricate,
let's understand it simply.
Consider a lock-and-key
mechanism: every lock necessitates a specific key to open or close it. Using
any other key renders it ineffective. Each lock features a unique shape within
the hole for key insertion. A key is crafted to precisely fit this shape. Only
when the key perfectly aligns with the lock's shape does it open. Similarly,
molecular docking operates.
In every living organism, numerous enzymes govern cellular and bodily functions. These enzymes are proteins comprising amino acids. Each enzyme encompasses an active part responsible for a specific function. Enzymes possess distinct shapes, with up to 1000 amino acids in some cases. The arrangement of these amino acids creates particular cavities within enzymes. Only a specific molecule can fit into these cavities. For example, the enzyme amylase converts starch into maltose. Initially, the starch molecule fits into amylase's cavity before transforming into glucose. This cavity is referred to as the active site.
To comprehend these interactions,
software is utilized to ascertain if any molecule fits into a protein's cavity.
This process is termed molecular docking.
In molecular docking, the binding
affinity of any molecule with a protein or enzyme is determined. Through various
software applications, any molecule is docked within a protein to discern the
part or active site of the protein where target molecule docks.
The molecule interacts with
various amino acids in the active site of protein, involving hydrogen bonding
and hydrophobic bonding. Software then computes a binding energy based on these
interactions. The site where this binding energy is the lowest is typically a
perfect docking site where our molecule can fit.
What is the role of molecular docking in drug discovery?
Drug discovery is a lengthy
process, commencing with ideation and design. Researchers initially identify
the specific enzyme they need to target for any disease. This concept is
straightforward, as enzymes regulate body functions and cellular processes. So,
if a particular enzyme is blocked, it won't be able to perform its related
function. By altering the shape of a particular pocket or cavity, or deforming
it, the enzyme can be inhibited.
After identifying the target, scientists design molecules based on existing commercial drugs, natural products, or their expertise. These molecules can either block the enzyme or fit into the specific pocket.
Every drug encompasses numerous
functionalities, including aliphatic chains, aromatic rings, heterocyclic
rings, and other elements like chlorine, nitrogen, fluorine, etc. Scientists
may design approximately 1000 or more molecules, but only one may exhibit
potential for commercial availability. Alternatively, none may show potential,
or a promising molecule may fail in clinical trials.
Here molecular docking plays a
crucial role in drug discovery by:
1. Screening out potential
drug candidates: Molecular docking screens potential drugs from the
designed ones.
2. Selecting specific
functionalities and determining their positions: Molecular docking
identifies which functionalities enhance the drug's effect and their optimal
placement. For instance, positioning a chloro group at the para position of the
phenyl ring in a drug can significantly enhance its efficacy.
3. In cost-saving:
Molecular docking aids in identifying potent drugs, obviating the need to
synthesize every molecule. This translates to substantial cost savings for
industries and scientists.
4. In time-saving: Alongside
cost savings, molecular docking also saves time.
