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Related Concept Videos

Ligand Binding Sites02:40

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 Sites02:40

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...
Conserved Binding Sites01:49

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 analyses the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Ligand Binding and Linkage00:49

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 the...
Protein-protein Interfaces02:04

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 polypeptide...

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Updated: May 8, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Predicting and Decoding Allosteric Binding Sites Using Protein Language Models and Structure-Based Machine Learning:

Kamila Riedlová1, Vít Škrhák1, William G Gatlin2

  • 1Department of Software Engineering, Faculty of Mathematics and Physics, Charles University, Prague 11800, Czech Republic.

Journal of Chemical Theory and Computation
|May 7, 2026
PubMed
Summary
This summary is machine-generated.

Predicting allosteric binding sites is challenging. This study reveals that protein energy landscape frustration explains why some binding sites are easier to predict than others, impacting drug discovery.

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Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
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A Protocol for Computer-Based Protein Structure and Function Prediction
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Published on: November 3, 2011

Area of Science:

  • Computational biology
  • Structural bioinformatics
  • Protein dynamics

Background:

  • Allosteric binding site prediction is difficult for computational and structure-based methods.
  • The reasons for this predictive asymmetry are not well understood.

Purpose of the Study:

  • To investigate the factors determining binding site predictability.
  • To understand the difference in predictability between orthosteric and allosteric sites.

Main Methods:

  • Utilized a dual framework combining a protein language model and P2Rank.
  • Analyzed 453 human kinases and employed energy landscape frustration analysis.
  • Applied an explainable AI approach for physical interpretability.

Main Results:

  • Both methods accurately predicted orthosteric ATP-binding sites but struggled with allosteric sites.
  • Predictive success correlates with the energetic embedding of binding sites.
  • Allosteric sites are in neutrally frustrated regions, unlike minimally frustrated orthosteric sites.

Conclusions:

  • Energy landscape frustration influences algorithmic visibility of binding sites.
  • This framework provides insights into binding site organization and prediction limitations.
  • Identifies energy landscape frustration as a key factor in predicting binding site detectability.