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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...

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...

Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Protein Folding

Protein Folding

Conservation of Protein Domains

Conservation of Protein Domains

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Related Experiment Video

Updated: Sep 11, 2025

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Functional sub-states link conformational landscapes and protein evolution.

Morito Sakuma¹, Karol Buda¹, H Adrian Bunzel²

¹Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.

Current Opinion in Structural Biology

|August 17, 2025

Summary

Protein flexibility generates diverse structures, influencing function. Mutations can alter these structures, driving the evolution of new protein functions by selecting specific functional sub-states.

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Last Updated: Sep 11, 2025

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

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Published on: July 14, 2015

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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

Area of Science:

Biochemistry
Molecular Biology
Evolutionary Biology

Background:

Proteins exhibit intrinsic conformational flexibility, leading to structural heterogeneity and the formation of conformational ensembles.
These ensembles can contain distinct functional sub-states, which are crucial for protein activity and regulation.

Purpose of the Study:

To present a conceptual framework on the significance of functional sub-states in protein evolution.
To explore how evolutionary processes select for specific functional sub-states.
To review current understanding and future directions in studying protein functional sub-states.

Main Methods:

Conceptual review integrating existing literature.
Highlighting key experimental studies on functional sub-states.
Discussing evolutionary trajectories and transitions between sub-states.

Main Results:

Mutations can reshape protein conformational landscapes, altering the distribution of functional sub-states.
Evolutionary selection can act on these altered distributions, leading to novel functions.
Key studies demonstrate the existence and importance of functional sub-states.

Conclusions:

Functional sub-states are critical determinants of protein function and evolution.
Understanding transitions between sub-states provides insights into evolutionary pathways.
Advanced techniques are needed to fully elucidate the dynamics and evolution of functional sub-states.