Studying the Flexibility of Undecaprenyl Pyrophosphate Synthase for Drug Design
Author Information
Author(s): Wm. Sinko, César de Oliveira, Sarah Williams, Adam Van Wynsberghe, Jacob D. Durrant, Rong Cao, Eric Oldfield, J. Andrew McCammon
Primary Institution: University of California San Diego
Hypothesis
Can molecular dynamics simulations reveal conformational states of undecaprenyl pyrophosphate synthase that are important for inhibitor design?
Conclusion
The study found that different classes of inhibitors can bind to specific conformational states of undecaprenyl pyrophosphate synthase, which are rarely sampled in simulations.
Supporting Evidence
- Undecaprenyl pyrophosphate synthase is crucial for bacterial cell wall biosynthesis.
- The study identified that the protein has highly mobile binding pockets.
- Different inhibitors can bind to different conformational states of the enzyme.
- The first complete apo structure of E. coli UPPS was described.
- Simulations revealed that the active site volume changes significantly upon ligand binding.
Takeaway
Researchers used computer simulations to see how a protein important for bacteria can change shape, which helps in designing new medicines to fight infections.
Methodology
The study involved long molecular dynamics simulations, docking studies, and crystallography to analyze the behavior of undecaprenyl pyrophosphate synthase.
Limitations
The study's findings are based on simulations and may not fully capture the complexity of the protein's behavior in vivo.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website