Related Experiment Video
Updated: Jul 30, 2026
10:40
Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
SH2 binding site comparison: a new application of the SURFCOMP method
Christian Hofbauer1, András Aszódi
1In Silico Sciences Unit, Informatics and Knowledge Management, Novartis Institutes for BioMedical Research Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria.
Journal of Chemical Information and Modeling
|April 6, 2005
Summary
This study introduces SURFCOMP, a method to detect differences in protein binding sites. This can improve drug specificity and reduce side effects by targeting specific protein family members.
Area of Science:
- Computational biology
- Structural bioinformatics
- Drug discovery
Background:
- Drug specificity is crucial for minimizing side effects, especially when targeting proteins within a family.
- Exploiting subtle structural differences in binding sites is key to achieving selective drug action.
- Analyzing physicochemical properties on molecular surfaces aids in identifying these differences.
Purpose of the Study:
- To demonstrate the efficacy of the SURFCOMP method for detecting differences between closely related protein binding sites.
- To apply SURFCOMP to the SH2 domains of Sap and Eat-2 proteins.
- To explore how identified binding site differences can inform drug specificity.
Main Methods:
- Utilized SURFCOMP, a local surface similarity detection algorithm.
- Analyzed the physicochemical properties mapped onto the molecular surfaces of protein binding sites.
- Focused on the SH2 domains of Sap and Eat-2, known signal transduction molecules.
Main Results:
- SURFCOMP successfully detected differences between the binding sites of the highly similar Sap and Eat-2 proteins.
- The identified structural variations provide a basis for understanding the differential specificities of these proteins.
- This highlights the potential for targeted drug development.
Conclusions:
- SURFCOMP is an effective tool for identifying subtle structural variations in protein binding sites.
- Understanding these differences is critical for designing specific drug candidates.
- This approach can advance the development of safer and more effective therapeutics.
Related Concept Videos
02:40Ligand 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...
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...
01:49Conserved 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...
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...
00:49Ligand 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...
01:192D NMR: Heteronuclear Single-Quantum Correlation Spectroscopy (HSQC)
Heteronuclear single-quantum correlation spectroscopy (HSQC) is a 2D NMR technique that reveals one-bond correlations between hydrogen and a heteronucleus. The HSQC experiment is similar to the heteronuclear correlation experiment (HETCOR) but is more sensitive. In the HSQC spectrum, the proton chemical shift is plotted on the horizontal F2 axis, while the 13C chemical shift is plotted on the vertical F1 axis. The corresponding proton and 13C spectra are also shown. The HSQC contour plot does...
01:49Conserved 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...
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...