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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...

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:

Conserved Binding Sites

Conserved Binding Sites

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.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Protein-Drug Binding: Determination Methods

Protein-Drug Binding: Determination Methods

Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...

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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

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Published on: July 25, 2013

Iterative Knowledge-Based Scoring Function for Protein-Ligand Interactions by Considering Binding Affinity

Xuejun Zhao¹, Hao Li¹, Keqiong Zhang¹

¹School of Physics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China.

The Journal of Physical Chemistry. B

|October 12, 2023

Summary

This summary is machine-generated.

We improved the ITScore scoring function to ITScoreAff by incorporating binding affinity data. This enhanced model shows superior performance in predicting protein-ligand interactions for drug design.

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Area of Science:

Computational chemistry
Structural biology
Drug discovery

Background:

Scoring functions are crucial for structure-based drug design.
Knowledge-based scoring functions offer a balance of applicability and efficiency.
Current knowledge-based functions struggle with accurate binding affinity prediction.

Purpose of the Study:

To develop an improved knowledge-based scoring function, ITScoreAff, by integrating experimental binding affinity data.
To enhance the prediction accuracy of protein-ligand interactions.

Main Methods:

Developed ITScoreAff by modifying the iterative knowledge-based scoring function ITScore.
Trained ITScoreAff on a large dataset of 6216 protein-ligand complexes with structural and affinity data.
Evaluated ITScoreAff against 40 other scoring functions using the CASF-2016 benchmark.

Main Results:

ITScoreAff demonstrated superior performance in docking, ranking, and screening power compared to existing methods.
Achieved an 85.3% success rate in docking power and a 0.723 correlation coefficient in scoring power.
Showcased the best screening power when considering the top 10% of ranked compounds.

Conclusions:

ITScoreAff represents a significant improvement over traditional and machine learning scoring functions.
The integration of binding affinity data enhances the robustness and predictive power of knowledge-based scoring functions.
ITScoreAff shows promise for more accurate structure-based drug design and virtual screening.