How Ligand Binding Affects Dihydrofolate Reductase
Author Information
Author(s): Hu Zengjian, Bowen Donnell, Southerland William M, del Sol Antonio, Pan Yongping, Nussinov Ruth, Ma Buyong
Primary Institution: Howard University College of Medicine
Hypothesis
How do ligand binding and circular permutation affect the residue interaction network in dihydrofolate reductase (DHFR)?
Conclusion
Ligand binding modifies the residue interaction network in DHFR, leading to shorter average communication paths within the protein.
Supporting Evidence
- DHFR is a clinically important enzyme and the target of antifolate drugs.
- Breaking the peptide chain at different points leads to differentiated behavior near the enzyme active site.
- Network analysis reveals that ligand binding has 'network-bridging effects' on the DHFR structure.
Takeaway
This study looks at how a protein called DHFR communicates inside itself when a molecule binds to it. It finds that binding helps the protein work better by making communication faster.
Methodology
The study used molecular dynamics simulations and network analysis to investigate the effects of ligand binding and circular permutations on DHFR.
Limitations
The study does not assess the folding ability of the systems with respect to whether they can achieve a native-like state.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website