Calculating Probability of Ligand-Protein Binding at Equilibrium

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SUMMARY

The discussion focuses on calculating the probability of a monovalent ligand binding to a protein with six independent binding sites at equilibrium, given a dissociation constant (KD) of 1 nM and a ligand concentration (L0) of 2 nM. Participants highlight the importance of the Scatchard equation, which relates the ratio of bound ligand to free ligand concentration, and the association constant (Ka). The challenge lies in applying these concepts to derive the numerical probability of at least five ligands binding to the protein.

PREREQUISITES
  • Understanding of ligand-protein interactions and binding kinetics
  • Familiarity with the Scatchard equation and its components
  • Knowledge of dissociation constant (KD) and association constant (Ka)
  • Basic probability theory and statistical methods
NEXT STEPS
  • Study the Scatchard equation and its applications in biochemistry
  • Learn how to calculate probabilities in ligand binding scenarios
  • Explore the relationship between KD and Ka in binding affinity
  • Investigate physical chemistry resources for probability equations related to ligand binding
USEFUL FOR

This discussion is beneficial for biochemists, molecular biologists, and students studying protein-ligand interactions, particularly those interested in binding kinetics and statistical analysis of biochemical systems.

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Homework Statement



A monovalent ligand binds to a protein with six in independent, identical binding sites. What is the probability that a given protein molecule is bound by at least five ligand molecules at equilibrium if K^{\mu}_{D} = 1nM and L_{0}=2nM (constant)?


Homework Equations



I don't really know what equations to use to get started on this.


The Attempt at a Solution



I suppose this would be more of a probability or statistics based problem, but I have to take into consideration the protein binding affinity and ligand concentration. I know K_{D} is K_{off}/K_{on}, so that would be a measure of the probability of binding to anyone spot. The initial ligand concentration also determines the probability of binding since it allows for more ligand to be bound to the protein binding sites. But I don't know how to use these definitions to create a mathematical way to find the actual numerical probability.

I would appreciate any help.
 
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Quickdry135 said:

Homework Statement



A monovalent ligand binds to a protein with six in independent, identical binding sites. What is the probability that a given protein molecule is bound by at least five ligand molecules at equilibrium if K^{\mu}_{D} = 1nM and L_{0}=2nM (constant)?


Homework Equations



I don't really know what equations to use to get started on this.


The Attempt at a Solution



I suppose this would be more of a probability or statistics based problem, but I have to take into consideration the protein binding affinity and ligand concentration. I know K_{D} is K_{off}/K_{on}, so that would be a measure of the probability of binding to anyone spot. The initial ligand concentration also determines the probability of binding since it allows for more ligand to be bound to the protein binding sites. But I don't know how to use these definitions to create a mathematical way to find the actual numerical probability.

I would appreciate any help.

Have you studied Scatchard plots or the Scatchard equation or the Eadie-Scatchard equation?
 
The scatchard equation is (r/c) = Ka*n - Ka*r, where r is the ratio of the concentration of bound ligand to total available binding sites, c is the concentration of free ligand, Ka is the association constant, and n is the number of binding sites per protein, right? So through this I could find the ratio of bound ligand to total available binding sites under the given ligand concentration and Kd (the inverse would be Ka). Which would be 4 or 24/6. But how would I use this ratio to determine the probability of a protein binding to 5 or more ligand molecules?

Thanks for replying, by the way.
 
Last edited:
Sorry, I think I misunderstood your question. I've never calculated probabilities in that way before. Perhaps someone over at mathematics can help.
 
Ok thanks anyway, I know there's a probability equation pertaining to this in physical chemistry, but for the life of me I can't remember it or find it in my book.
 

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