Why are Binding Kinetics Important? 

Binding kinetics have been studied for many years and make up the basis of pharmacological theory today. Whilst all pharmaceutical drugs are different, the binding kinetics have many similarities. 

The term binding kinetics refers to how quickly a compound binds to its target and the speed at which it dissociates from it. Binding kinetics measure the on-rate and the off-rate but have historically been challenging to measure. This article will explain the fundamentals of binding kinetics and how they work. 

The Importance of Binding Affinity 

The binding affinity of a drug is inextricably linked to binding kinetics. The binding affinity refers to the levels of drugs needed to occupy 50% of the target molecules at equilibrium. This number is the target occupancy, used to predict in-vivo efficacy.  

The residence time is a quantitative value referring to how long it takes for drug-receptors to reach target occupancy.  

The Importance of Binding Kinetics in Affinity Measurements 

The importance of binding kinetics is based on the fact that the time to reach equilibrium is dependent on the dissociation time. When the opposing rates are equal, a binding interaction is at equilibrium. Because association takes place first for dissociation to occur. This is why full binding kinetics data is required to effectively measure binding affinity. When using binding kinetics, meeting an equilibrium isn’t required and therefore it can be a much faster method. 

Binding Kinetics in Drug Discovery 

Accurate and fast measurement of binding affinity is critically important in the drug discovery process. If the actual affinity is above what is measured then patients may risk overdose in clinical drug trials. Similarly, if it is lower than recorded potentially life-saving drugs could be missed because of under-dosing.  

Binding kinetics differentiate medication by informing dose-response relationships. This means that physiological effectors can be appropriately counteracted by drug concentrations.  

Binding kinetics are intrinsically linked to the translation of drug action to safety, efficacy, and duration of response outcomes.  

How to Measure Binding Kinetics 

Establishing an understanding of binding kinetics is critical for developing drug molecules. To do this, equilibrium constants must be established. Koff is the dissociation constant in min-1.  Kon is the association constant in inverse minutes multiplied by inverse concentration. KD is computed from Koff/Kon. Expressed in Molar units 

Gator Bio BLI provides a simple means of measuring kinetics. Using real-time data, binding kinetics (Kon and Koff) and affinity values (KD) can be measured. Because BLI offers insight into dissociation, association rates, and affinity value it can help predict the activity of biomolecules in vivo.  

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