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The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:

The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Protein-Drug Binding: Determination Methods

Protein-Drug Binding: Determination Methods

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
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Related Experiment Video

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Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry

Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry

Published on: September 13, 2014

Protein-ligand binding affinity by nonequilibrium free energy methods.

Benjamin P Cossins¹, Sebastien Foucher, Colin M Edge

¹School of Chemistry, University of Southampton, Highfield, Southampton, UK.

The Journal of Physical Chemistry. B

|November 1, 2008

Summary

Nonequilibrium (NE) free energy methods, like the replica exchange method using Bennett

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Published on: November 21, 2017

Area of Science:

Computational Chemistry
Biophysics
Drug Discovery

Background:

Nonequilibrium (NE) free energy methods offer parallelization for computational tasks.
Their application to protein-ligand binding free energy calculations remains underexplored.
Previous work identified promising NE protocols comparable to equilibrium methods.

Purpose of the Study:

To evaluate a specific NE protocol, replica exchange with Bennett's acceptance ratio (RENE), for protein-ligand binding free energy prediction.
To compare RENE performance against traditional equilibrium methods (RETI) using established systems.
To assess the feasibility of large-scale distributed computing for these simulations.

Main Methods:

Application of the RENE protocol to congeneric inhibitors binding to neuraminidase and cyclooxygenase-2.
Comparison of RENE simulation results with existing RETI data for the same systems.
Execution of NE calculations on a distributed network of low-performance desktop computers (Condor pool).

Main Results:

RENE achieved predictive accuracy comparable to RETI but in less than half the wall clock time.
Non-replica exchange NE methods showed significantly lower predictive power.
RENE successfully identified localized regions of rapid free energy gradient changes without prior knowledge.

Conclusions:

The RENE protocol is suitable for predicting protein-ligand binding free energies.
RENE offers significant advantages in speed and efficiency over conventional equilibrium methods.
Distributed computing with NE methods provides a powerful and practical approach for drug discovery.