We have tested a computational protocol based on molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) free-energy calculations to examine the detailed microscopic structures and binding free energies for the pyruvate dehydrogenase multienzyme complex (PDHc) E1 binding with its ligands (cofactor and inhibitors). The calculated binding free energies are all in good agreement with available experimental data, with an average absolute deviation of ∼0.7 kcal/mol, suggesting that the computational protocol tested may be valuable in future rational design of new, more potent inhibitors of PDHc E1.
|Number of pages||5|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Sep 15 2007|
Bibliographical noteFunding Information:
The research was supported in part by National Basic Research Program of China (No. 2003CB114400), National Natural Science Foundation of China (No. 20602014, No. 20503008, No. 20372023), National Institutes of Health (R01DA013930), and the Center for Computational Sciences at University of Kentucky.
- Binding affinity
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry