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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.
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Protein-protein Interfaces

Protein-protein Interfaces

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Related Experiment Video

Updated: Apr 28, 2026

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

Computational analysis of protein hotspots.

Chao-Yie Yang¹, Shaomeng Wang¹

¹Departments of Internal Medicine and Medicinal Chemistry, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0934.

ACS Medicinal Chemistry Letters

|June 6, 2014

Summary

Computational methods can identify protein hotspots for drug design. The cosolvent mapping method efficiently finds hotspots and estimates binding energy, complementing the precise free energy double-decoupling method for enhanced drug discovery.

Keywords:

Computational analysis binding free energy cosolvent mapping method double-decoupling method protein hotspots

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

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

Published on: July 25, 2013

Area of Science:

Computational chemistry
Structural biology
Drug discovery

Background:

Protein hotspots are crucial for drug design.
Accurate binding free energy calculations are vital for understanding molecular interactions.

Purpose of the Study:

To computationally analyze binding free energies of protein hotspots.
To compare the efficacy of the free energy double-decoupling and cosolvent mapping methods.

Main Methods:

Computational analysis of two known hotspots in thermolysin.
Application of the free energy double-decoupling method.
Application of the cosolvent mapping method.

Main Results:

The free energy double-decoupling method accurately determines binding free energy for various probe-hotspot combinations.
The cosolvent mapping method effectively identifies known protein hotspots and provides reliable binding free energy estimates.
Cosolvent mapping is less computationally expensive than the double-decoupling method.

Conclusions:

Cosolvent mapping is a valuable tool for initial hotspot identification and energy estimation in drug design.
Combining cosolvent mapping with the double-decoupling method offers a powerful strategy for drug discovery.
These computational approaches provide critical insights for designing effective therapeutics.