Theoretical calculation of the binding free energies for pyruvate dehydrogenase E1 binding with ligands

Ying Xiong; Yongjian Li; Hongwu He; Chang Guo Zhan

doi:10.1016/j.bmcl.2007.06.095

Theoretical calculation of the binding free energies for pyruvate dehydrogenase E1 binding with ligands

Ying Xiong, Yongjian Li, Hongwu He, Chang Guo Zhan

Pharmaceutical Sciences

Producción científica: Article › revisión exhaustiva

17 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	5186-5190
Número de páginas	5
Publicación	Bioorganic and Medicinal Chemistry Letters
Volumen	17
N.º	18
DOI	https://doi.org/10.1016/j.bmcl.2007.06.095
Estado	Published - sept 15 2007

Nota bibliográfica

Funding 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.

Financiación

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.

Financiadores	Número del financiador
National Institutes of Health (NIH)
National Institute on Drug Abuse	R01DA013930
National Natural Science Foundation of China (NSFC)	20372023, 20503008, 20602014
National Basic Research Program of China (973 Program)	2003CB114400

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2007.06.095

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title = "Theoretical calculation of the binding free energies for pyruvate dehydrogenase E1 binding with ligands",

abstract = "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.",

keywords = "Binding, Binding affinity, Dehydrogenase, Herbicide, Inhibitor, Modeling",

author = "Ying Xiong and Yongjian Li and Hongwu He and Zhan, \{Chang Guo\}",

note = "Funding 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. ",

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AU - Xiong, Ying

AU - Li, Yongjian

AU - He, Hongwu

AU - Zhan, Chang Guo

N1 - Funding 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.

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Y1 - 2007/9/15

N2 - 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.

AB - 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.

KW - Binding

KW - Binding affinity

KW - Dehydrogenase

KW - Herbicide

KW - Inhibitor

KW - Modeling

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Theoretical calculation of the binding free energies for pyruvate dehydrogenase E1 binding with ligands

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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