Related Experiment Video
Updated: Jun 20, 2026
14:34
A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
Published on: April 3, 2026
Structural artifacts in protein-ligand X-ray structures: implications for the development of docking scoring
Chresten R Søndergaard1, Alison Elizabeth Garrett, Tommy Carstensen
1School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Journal of Medicinal Chemistry
|August 29, 2009
Summary
Crystal contacts in protein-ligand complexes can affect docking scoring functions. Our analysis reveals 36% of ligands are influenced by these crystal artifacts, impacting function performance.
Area of Science:
- Computational chemistry
- Structural biology
- Drug discovery
Background:
- High-resolution protein-ligand structures are crucial for developing docking scoring functions.
- Experimental binding affinities are measured in solution, while structures are determined via X-ray crystallography.
- Scoring functions must reconcile solution binding energies with crystal environments.
Purpose of the Study:
- To analyze crystal-induced artifacts and water-mediated contacts in protein-ligand complexes.
- To demonstrate the impact of these artifacts on protein-ligand scoring function performance.
- To provide a tool for identifying crystal contacts.
Main Methods:
- Analysis of protein-ligand complexes from the PDBBind 2007 refined dataset.
- Evaluation of the influence of crystal contacts on scoring function performance.
- Development of a web server for crystal contact detection.
Main Results:
- 36% of ligands in the dataset were found to be influenced by crystal contacts.
- Crystal contacts were shown to affect the performance of protein-ligand scoring functions.
- A web server (http://enzyme.ucd.ie/LIGCRYST) was developed for detecting crystal contacts.
Conclusions:
- Crystal-induced artifacts are prevalent in protein-ligand crystal structures.
- These artifacts can significantly impact the accuracy of docking scoring functions.
- Awareness and detection of crystal contacts are important for reliable scoring function development.
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...
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...
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...
02:18The 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: