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ConfGen: a conformational search method for efficient generation of bioactive conformers
K Shawn Watts1, Pranav Dalal, Robert B Murphy
1Schrodinger, LLC, 101 SW Main Street, Suite 1300, Portland, Oregon 97204, USA.
Journal of Chemical Information and Modeling
|April 9, 2010
Summary
ConfGen efficiently generates bioactive ligand conformations using physics-based calculations and heuristics. It achieves high accuracy with minimal computation, aiding drug discovery and pharmacophore modeling.
Area of Science:
- Computational chemistry
- Molecular modeling
- Drug discovery
Background:
- Generating accurate ligand conformations is crucial for molecular modeling and drug design.
- Existing methods may lack efficiency in exploring the conformational space of ligands.
- Bioactive conformer generation requires balancing speed and accuracy.
Purpose of the Study:
- To introduce ConfGen, a novel conformational search method for efficient bioactive conformer generation.
- To define and characterize different operational modes of ConfGen.
- To validate ConfGen's performance against established methods using diverse crystal structures.
Main Methods:
- ConfGen combines physics-based force field calculations with empirical heuristics.
- Four distinct modes offer varying speed-quality trade-offs.
- Ligands from 667 crystal structures were used for validation.
Main Results:
- ConfGen achieves high recovery rates (96-99%) of bioactive conformations.
- The fastest mode uses 0.5s/ligand generating 14.3 conformers.
- Even the most intensive mode takes only 8s/ligand.
Conclusions:
- ConfGen demonstrates superior efficiency compared to competing programs.
- Its performance is suitable for downstream applications like pharmacophore modeling.
- The method effectively prioritizes ligand conformational space for drug discovery.
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