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Updated: Jan 12, 2026
14:37
Modeling an Enzyme Active Site using Molecular Visualization Freeware
Published on: December 25, 2021
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Modeling protein-small molecule conformational ensembles with PLACER.
Ivan Anishchenko1,2, Yakov Kipnis1,2,3, Indrek Kalvet1,2,3
1Department of Biochemistry, University of Washington, Seattle, WA 98105.
Summary
We developed PLACER, a graph neural network for protein-ligand atomistic conformational ensemble resolution. This tool rapidly generates diverse molecular structures, improving enzyme design and predicting protein-small molecule interactions.
Area of Science:
- Computational chemistry
- Structural biology
- Artificial intelligence in drug discovery
Background:
- Modeling conformational heterogeneity in protein-small molecule interactions is crucial but challenging.
- Atomic-level descriptions offer potential advantages in speed and generality for probing interactions in folded states.
Purpose of the Study:
- To develop a novel computational tool for modeling protein-small molecule interactions.
- To generate accurate atomic-level conformational ensembles for small molecules and protein-ligand complexes.
- To enhance enzyme design by assessing active site preorganization and accuracy.
Main Methods:
- Developed PLACER (protein-ligand atomistic conformational ensemble resolver), a graph neural network model.
- Trained PLACER on atomic positions from corrupted structures in the Cambridge Structural Database and Protein Data Bank.
- Utilized PLACER for generating small molecule structures, protein side chains, and protein-small molecule docking ensembles.
Main Results:
- PLACER accurately generates diverse organic small molecule structures based on composition and bonding.
- The model effectively builds small molecule and protein side chain structures for docking.
- Enzyme design using PLACER for active site assessment led to higher success rates and activities, including a retroaldolase with a kcat/KM of 11,000 M-1min-1.
Conclusions:
- PLACER provides a rapid and stochastic method for generating conformational ensembles.
- The tool is effective for both small molecule and protein-ligand systems.
- PLACER shows significant promise for improving enzyme design and predicting molecular interactions.
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