Discovering how to consistently and reliably find a binding mechanism for drug targets has challenged researchers for years. Now, there is a new method that researchers can use to discover the optimum molecular binding of a drug to a target cell. Molecule binding is a critical factor in determining how well a drug will work in a living organism. For a binding to occur, a drug must be able to physically attach to its target protein and have an electrostatic attraction to bind them together. When molecular binding occurs, it is called intermolecular force. Intermolecular force is obtained by a chemical bond created when the atoms physically attach to each other through electrostatic attraction.
All atoms are composed of a nucleus that has a positive electric charge, which is then surrounded by electrons that have a negative electric charge. Atoms naturally seek to obtain an electrically neutral status by absorbing, discarding, or sharing electrons with another atom. When they share electrons with another atom, they form a chemical bond called an intramolecular force. Atoms form together in a specific structure to create a molecule — in this case, a drug molecule — which then seeks to attach to a specific target protein, or receptor molecule, that is a part of the cell it is intended to interact with and deliver the drug.
The strength of the molecular binding between the drug and the drug-receptor of a cell establishes how well the drug will do its job. Specialized lab equipment called an isothermal titration calorimeter can be used to determine how strong the molecular binding is for any given drug. This process is called isothermal titration calorimetry (ITC).
An isothermal titration calorimeter is comprised of two identical metal alloy or gold cells that are thermally efficient at conducting electricity, as well as chemically inert. These cells are then encased in an adiabatic jacket. Specialized electric circuits are used to observe temperature differences between the reference cell, which is either filled with water or a buffering agent, and the sample cell containing the drug molecule, which is already attached through molecular binding to the target cell molecule.
Then, a special molecule that binds to metal, called a ligand, is introduced into the reference cell, causing an exothermic reaction that heats the reference cell, which then activates a feedback circuit that heats the sample cell in precise measurements. The exothermic observations are plotted on a graph and a formula is created to determine how much power is needed to maintain equal temperatures between the sample and the reference cells versus time.
When evaluating the strengths of these challenging interactions, certain technologies offer superior measuring techniques for in-solution binding affinities. Monolith is a cutting-edge technique that eases the volume requirements of standard approaches like isothermal calorimetry and distinguishes the binding affinity of ligands for specific proteins.
With the thermodynamics of the molecular binding, researchers can discover more ways to improve the molecular binding of medicinal compounds, which, in turn, can provide the ability to discover new drugs that will be more efficacious when administered to patients suffering from forms of various illnesses.