How Drugs Change Shape When Binding to Proteins
Author Information
Author(s): Günther Stefan, Senger Christian, Michalsky Elke, Goede Andrean, Preissner Robert
Primary Institution: Institute for Biochemistry, Charité
Hypothesis
How well is a bound drug represented by a limited number of computed conformers?
Conclusion
Single drugs adopt multiple bioactive conformations if they interact with different target proteins.
Supporting Evidence
- 70% of drugs are represented by a generated conformer with a root mean square deviation (rmsd) lower than 1 Å.
- The majority of drugs is well represented by a predefined low number of conformers (up to 100).
- 46% of the inspected drugs are assigned to more than one computed conformer indicating multiple bioactive states.
Takeaway
Drugs can change their shape when they attach to different proteins, and we can use a small number of shapes to understand how they work.
Methodology
The study involved generating 9600 drug conformers and comparing them to 193 approved drugs to assess how well they represent the bound states.
Limitations
The study may not account for all possible conformations due to the limitations of the conformer generation methods.
Digital Object Identifier (DOI)
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