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Drug-like bioactive structures and conformational coverage with the LigPrep/ConfGen suite: comparison to programs MOE
1Vernalis (R&D) Ltd., Granta Park, Abington, Cambridge CB21 6GB, United Kingdom. i.chen@vernalis.com
Journal of Chemical Information and Modeling
|April 29, 2010
Summary
This study evaluates LigPrep/ConfGen software for small molecule conformational sampling. A new "ConfGen Optimized" protocol improves accuracy in reproducing bioactive structures, offering a flexible tool for drug design.
Area of Science:
- Computational chemistry
- Drug discovery and design
Background:
- Computational conformational sampling is crucial for small molecule modeling in pharmaceuticals.
- The LigPrep/ConfGen software suite is widely used for this purpose.
Purpose of the Study:
- To thoroughly examine LigPrep/ConfGen's conformational models for drug-like compounds.
- To compare LigPrep/ConfGen with MOE and Catalyst.
- To guide users in selecting optimal ConfGen protocols and parameters.
Main Methods:
- Testing conformational sampling protocols by reproducing known bioactive ligand structures.
- Analyzing the size, coverage, and diversity of generated conformational models.
- Measuring relative computation times.
- Developing and testing a new 'ConfGen Optimized' protocol.
Main Results:
- The 'ConfGen Optimized' protocol reproduced 80% of bioactive structures within 1 Å, outperforming the default ConfGen Fast protocol (66%).
- Heuristics penalizing folded conformers were found to hinder the reproduction of certain binding modes.
- LigPrep/ConfGen demonstrated significant flexibility and utility in molecular modeling.
Conclusions:
- LigPrep/ConfGen is a valuable and flexible tool for molecular modeling.
- The 'ConfGen Optimized' protocol offers improved accuracy for reproducing bioactive structures.
- Consideration of folded conformer reproduction is important for accurate binding mode analysis.
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