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

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Pages (from-to)	5186-5190
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2007.06.095
State	Published - Sep 15 2007

Bibliographical 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.

Keywords

Binding
Binding affinity
Dehydrogenase
Herbicide
Inhibitor
Modeling

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

Cite this

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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.

PY - 2007/9/15

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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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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